Biofouling resistant coatings and methods of making and using the same

ABSTRACT

Disclosed herein are compositions to use in biofouling-resistant coatings, biofouling-resistant coatings, methods of making biofouling-resistant coatings, biofouling-resistant devices, and methods of making biofouling-resistant devices.

CROSS-REFERENCE

This application claims benefit of U.S. Provisional Patent ApplicationNo. 62/593,645, filed on Dec. 1, 2017, the contents of which are fullyincorporated by reference herein.

BACKGROUND

Hospital acquired infections (HAIs) cause over 100,000 deaths per yearand over $30 billion in direct healthcare cost. In some cases, medicaldevices implanted into the body are the source of the HAI. Planktonicbacteria adhere to the surface of the medical devices and begin to growinto resilient biofilms that become more resistant to antibiotics anddisinfecting agents than in the planktonic state.

SUMMARY

Described herein, in certain embodiments, are compositions to use inbiofouling-resistant coatings, biofouling-resistant coatings, methods ofmaking biofouling-resistant coatings, biofouling-resistant devices, andmethods of making biofouling-resistant devices.

In one aspect, described herein is a compound of Formula (I):

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—;    -   L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O⁻, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and R^(10b) is —(C═O)—C2-C6alkenyl,        —(S═O)—C2-C6alkenyl, or —(S═O)₂—C2-C6alkenyl.

In another aspect, described herein is a compound of Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

In another aspect, described herein is a compound of Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

Any combination of the groups described above or below for the variousvariables is contemplated herein. Throughout the specification, groupsand substituents thereof are chosen by one skilled in the field toprovide stable moieties and compounds.

In another aspect, described herein is a medical device coated with acompound of Formula (I), (II), or (III).

In another aspect, described herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with a phenylazide-based copolymer having a number-average molecular weight ofbetween about 10,000 and about 250,000.

In another aspect, described herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with a phenylazide-based copolymer having a number-average molecular weight ofbetween about 14,000 and about 21,000.

In another aspect, described herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1 and 1.5.

In another aspect, described herein is a method of preparing abiofouling-resistant medical device, comprising:

-   -   a) contacting a surface of a medical device with a mixture        comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the medical device of step a) with a        light source for a time sufficient to undergo photografting of        the charged or zwitterion copolymer onto the surface of the        medical device, thereby making the biofouling-resistant medical        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        10,000 and about 250,000.

In another aspect, described herein is a method of preparing abiofouling-resistant medical device, comprising:

-   -   c) contacting a surface of a medical device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   d) treating the surface of the medical device of step a) with a        light source for a time sufficient to undergo photografting of        the charged or zwitterion copolymer onto the surface of the        medical device, thereby making the biofouling-resistant medical        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        14,000 and about 21,000.

In another aspect, described herein is a method of preparing a chargedor zwitterion copolymer modified biofouling-resistant device comprising:

-   -   a) contacting a surface of a silicon-based device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the        silicon-based device, thereby generating the charged or        zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer.

In another aspect, described herein is a method of preparing a chargedor zwitterion copolymer modified biofouling-resistant device comprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        10,000 and about 250,000.

In another aspect, described herein is a method of preparing a chargedor zwitterion copolymer modified biofouling-resistant device comprising:

-   -   c) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   d) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        14,000 and about 21,000.

In yet another aspect, described herein is a method for synthesizing acompound of Formula (II) comprising: reacting a compound of Formula (IV)or a salt or solvate thereof with a compound of Formula (V):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) and Formula (V) are each        independently charged or zwitterionic.

In another aspect, described herein is a method for synthesizing acompound of Formula (III) comprising: reacting a compound of Formula(IV) or a salt or solvate thereof with a compound of Formula (VI):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In one aspect, also described herein is a charged or zwitterioncopolymer modified biofouling-resistant device prepared by the methodcomprising:

-   -   a) contacting a surface of a silicon-based device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the        silicon-based device, thereby generating the charged or        zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer.

In another aspect, described herein is a charged or zwitterion copolymermodified biofouling-resistant device prepared by the method comprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        10,000 and about 250,000.

In another aspect, described herein is a charged or zwitterion copolymermodified biofouling-resistant device prepared by the method comprising:

-   -   c) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   d) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        14,000 and about 21,000.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying figures, which are incorporated in and constitute apart of this specification, illustrate several aspects and together withthe description serve to explain and not to limit the scope of currentdisclosure.

FIG. 1 illustrates representative photografting of poly(sulfobetainemethacrylate-co-perfluorophenylazide methacrylate) (PFPA-PSB copolymer)to a silicone surface.

FIG. 2A illustrates representative water advancing contact angle (upperimage) and receding contact angle (lower image) on an unmodifiedsilicone surface and (b) PFPA-PSB copolymer modified silicone surface.

FIG. 2B illustrates representative water advancing contact angle (upperimage) and receding contact angle (lower image) on a PFPA-PSB copolymermodified silicone surface.

FIG. 3A illustrates high density of Escherichia coli adhesion tounmodified silicone surface forming an elastic film, which fracturedupon surface drying.

FIG. 3B illustrates very low density of Escherichia coli adhesion topoly(sulfobetaine methacrylate-co-perfluorophenylazidemethacrylate)-modified silicone surface.

FIG. 4 illustrates the structure of PFPA-PSB copolymer.

FIG. 5A illustrates chemical structure of polydimethylsiloxane andpolysulfobetaine.

FIG. 5B illustrates XPS spectra of a PFPA-PSB modified PDMS substrate,showing the successful grafting of PSB on the organic substrate.

FIG. 5C illustrates evolution of water contact angle on PDMS substratestreated with 02 plasma or coated with PSB. The plasma treated PDMSsubstrate shows a rapid hydrophobic recovery, whereas, the PSB-modifiedPDMS substrate remains hydrophilic for an extended time.

FIG. 5D illustrates superhydrophilic properties of a wide spectrum ofhydrophobic organic substrates coated with PFPA-PSB copolymer, includingPDMS, Nylon 66, Polystyrene, polyvinyl chloride, and polyethylene.

FIG. 6A illustrates fluorescent images of uncoated and PFPA-PSB coatedPDMS substrates after incubation in a solution of AF-BSA. The brightspots are the protein molecules adsorbed to the PDMS substrates. Thecontrols show similar substrates incubated in Milli-Q water.

FIG. 6B illustrates pixel brightness of the PDMS substrates afterincubation in the protein solution shows that PFPA-PSB coated PDMSreduces the protein adsorption to ˜0.

FIG. 7A illustrates bright field images of 2D NIH/3T3 fibroblast culture0, 3, 6, 12, and 24 h post seeding on 96-well plates. Upper panelpresents the cell behavior on unmodified PDMS substrates, indicatingcell spreading initiated within ˜3 h post seeding. After ˜6 h, most ofthe cells are adhered and elongated on the unmodified PDMS substrate. Incontrast, the PFPA-PSB coated PDMS substrates do not permit celladhesion, maintaining the cells in the suspension form, which results incell aggregation within a few hours post seeding.

FIG. 7B illustrates live/dead staining of fibroblast cells after 24 hculture on the unmodified PDMS substrates shows that the cells adhere tothe unmodified PDMS substrate and remain viable; however, no live cellswere observed on PFPA-PSB coated PDMS substrates due to the lack ofadhesion. The negative control shows that all the cells are dead inDMSO.

FIG. 7C illustrates shape factor of cells defined as 4πA/P², where A isthe cell surface area and P is the perimeter, is a measure of spreading(elongation) tendency, which shows that the cells cultured on theunmodified PDMS substrate undergoes spreading (shape factor near zero)and those cultured on the PFPA-PSB coated PDMS substrates are almostspherical (shape factor near one).

FIG. 7D illustrates the percent of cells adhered to unmodified PDMSsubstrates, showing the proliferation of adhered cells, compared withalmost no cell attachment on PFPA-PSB modified PDMS substrates.

FIG. 8 illustrates the fluorescent microscopy images and quantitativeanalysis results from microbial adhesion after 24-48 hours of incubationon PFPA-PSB modified and unmodified surfaces.

FIG. 9A illustrates fluorescent images of Alexa Fluor 488-conjugatedfibrinogen flow in microfluidic channels. In 15 min, the intensity inuncoated channels significantly increases, showing a time-dependent,fast deposition of the protein in the channel. The PFPA-PSB coatedchannels remain resistant against protein adsorption, and upon rinsingwith Milli-Q water, no adsorbed protein can be observed.

FIG. 9B illustrates quantification of fibrinogen adsorption to PDMSmicrofluidic channels under flow. Without PFPA-PSB coating, the channelsundergo monotonic protein adsorption over time within 15 min; however,the PFPA-PSB coated channels do not show any significant proteinadsorption. The arbitrary intensity of fluorescent, a measure of proteinadsorption, shows that within 15 min, the fibrinogen deposition in theuncoated channel is ˜12000% more than the coated channel. Rinsing withwater washes all the proteins in the PFPA-PSB coated channel.

FIG. 9C illustrates adsorption of fluorescent (ATCC 25922GFP)Escherichia coli to the PDMS microfluidic channel under flow within 24 hshows that the uncoated channels permit a full coverage, whereas, thePFPA-PSB coated channels do not support bacterial adhesion.

FIG. 10A illustrates assessing the cytotoxicity of un-crosslinked PSB byadding a desirable amount of the polymer to the cell culture media of 2Dcultured fibroblast cells and measuring the metabolic activity of cellsusing MTT assay. Fluorescent intensity shows that the cells, regardlessof the PSB concentration (up to 1.6 mg mL⁻¹) are able to well metabolizethe cell membrane-permeable tetrazolium dye MTT, which attests to theinsignificant effect of PSB on the cell viability.

FIG. 10B illustrates live/dead staining of the fibroblast cells culturein 2D in the presence of un-crosslinked PBS shows a 100% viability ofcells within 72 h. The controls show the cells cultured in the absenceof PSB.

FIG. 10C illustrates the cytotoxicity of crosslinked PSB wasinvestigated by coating it on PDMS discs, followed by incubating thediscs in the cell culture media of 2D cultured fibroblast cells. Themetabolic activity of the cells does not show any significant differencewith the PSB-free control.

FIG. 10D depicts live/dead staining of the fibroblasts cells cultured inthe presence of crosslinked PSB shows that almost no cell is compromisedcompared to the PSB-free controls. Accordingly, un-crosslinked andcrosslinked PSB are both non-toxic for the cells, rendering thismaterial suitable for coating medical devices that are in contact withcells.

FIG. 11 illustrates contact angle measurements on control, PFPA-PSBmodified, and ethanol treated, PFPA-PSB modified samples.

FIG. 12 illustrates bacterial adhesion images on control, PFPA-PSBmodified, and ethanol treated, PFPA-PSB modified samples usingEscherichia coli. The values presented next to the images are theaverage percent area coverage for the three images taken on each sample.

FIG. 13 illustrates a timed drying experiment on control, PFPA-PSBmodified, and ethanol treated, PFPA-PSB modified samples using threedifferent types of commercial contact lenses.

Additional advantages of the invention will be set forth in part in thedescription which follows, and in part will be obvious from thedescription, or may be learned by practice of the invention. Theadvantages of the invention will be realized and attained by means ofthe elements and combinations particularly pointed out in the appendedclaims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION

Hospital acquired infections (HAIs) cause over 100,000 deaths per yearand over $30 billion in direct healthcare cost. Despite reduction ofHAIs in recent years through improved antiseptic technique, surgicalprocedure, and diagnosis, HAIs declines are slowing down indicating theneed for new preventative methods. In some instances, medical devicesimplanted into the body are the source of infection. It is estimatedthat 60-70% of HAIs are associated with the use of implantable medicaldevices. Planktonic bacteria adhere to the surface of the medicaldevices and begin to grow into resilient biofilms that become moreresistant to antibiotics and disinfecting agents than in the planktonicstate. As the biofilm grows and the cells continue to proliferate, theextracellular matrix scaffolding (made up of proteins andpolysaccharides) bursts open, releasing more bacteria into the body. Thebody can no longer stave off infection and strong antibiotics must beused to fight the infectious cells. The use of strong antibiotics hasled to the existence of antibiotic resistant bacteria, also known assuperbugs, which can no longer be treated with conventional antibiotics.

Without the initial adhesion of planktonic cells to the surface of amaterial, the biofilm formation is prevented or reduced. Severalresearchers have identified the attractive forces that cause organicmaterial to adhere to polymeric surfaces: hydrophobic interactions andelectrostatic interactions (van der Waals forces) between the organicmaterials and polymer surface. Using self-assembled monolayers,Whitesides et al. surveyed several functional groups to determinesurface functionalities that promote or hinder the non-specificadsorption of proteins. (Whitesides, G. M. A survey ofstructure-property relationships of surfaces that resist the adsorptionof protein. Langmuir, 2001, 17 (18), pp 5605-5620). The functionalgroups that exhibited the lowest adhesion were electrostatically neutralhydrophilic moieties that contained hydrogen bond donating groups. Fromthese design rules, many material coatings have been developed and shownto reduce adhesion of proteins and microorganisms. However, thesecoating are substrate dependent and/or require exotic reactionconditions that are not compatible for wide-scale use. In some cases,several polymers coatings and surface modifications have been developedto repel these interactions to reduce/prevent the formation of biofilmson surfaces. In some instances, the coating should have the followingchemical requirements to be used as an anti-fouling surface: a) thecoating should be hydrophilic; b) the coating should consist of mostlyof hydrogen bond acceptors; and c) the coating should beelectrostatically neutral. However, due to the water-solubility ofhydrophilic coatings, the coating material should be covalently bound tothe polymeric material for long-term effects.

In some instances, medical grade silicone is used in medical and healthcare industry. Its market currently undergoes a rapid growth and isprojected to reach $7.23 billion by 2021. Medical grade siliconegenerally includes polydimethylsiloxane (PDMS) fluids and elastomers.Due to their good chemical stability, matching mechanical propertieswith human tissues, and no-requirements for plasticizers, PDMSelastomers generally have excellent biocompatibility, and are used inmedical devices and biomedical implants such as catheters andpacemakers. PDMS elastomers also have high transparency and easyprocessability. Therefore, PDMS elastomers have found broad applicationsin fabricating microfluidic devices, which provide low-cost, simple, androbust systems for diagnosing diseases (Whitesides, G. M. The originsand the future of microfluidics. Nature 2006, 442 (7101), 368-373).However, PDMS elastomers also have a low surface energy of about 20mN/m. Bacteria, platelets, proteins, and other biomolecules tend toadhere to the hydrophobic surfaces of PDMS elastomers (Hron, P.Hydrophilisation of silicone rubber for medical applications. Polymerinternational 2003, 52 (9), 1531-1539). For silicone medical implants,bacterial adhesion and biofilm formation may lead to the failure ofmedical devices, severe infection, and even death of patients. Fordisease diagnosis devices based on PDMS microfluidics, proteins andother biomolecules fouling on the PDMS surfaces can significantly reducethe sensitivity of these devices, and may even lead to completedevice-failure if blocking of the microfluidic channels occurs (Zhou, J.et al. Recent developments in PDMS surface modification for microfluidicdevices. Electrophoresis 2010, 31 (1), 2-16).

Hydrophilic treatment of the PDMS surfaces was found to be one of thestrategies to alleviate or prevent the problem of biofouling (Keefe, A.J. et al. Suppressing surface reconstruction of superhydrophobic PDMSusing a superhydrophilic zwitterionic polymer. Biomacromolecules 2012,13 (5), 1683-1687). Some conventional methods of making PDMS surfaceshydrophilic include oxidation of the surfaces by oxygen plasma,UV-ozone, or corona discharge. However, these modifications are onlytemporary because PDMS has an extremely low glass transition temperatureof about −120° C. and therefore the PDMS chains are highly mobile atroom temperature. The PDMS chains are able to rearrange and recover thehydrophobic surface of PDMS elastomers within a time window of a fewhours. In some cases, other methods seeking to make long-lastinghydrophilic PDMS surfaces take many steps and involve radical reactionor polymerization. These steps have to be performed in closedcontainers, and/or under the protection of inert gas. Due to the highersolubility of oxygen relative to nitrogen in PDMS, in some instances ittakes long time to remove oxygen from PDMS so that the radical reactioncan proceed efficiently. These strict reaction conditions significantlyincrease the cost and limit industrial applicability of these reactions.

In some embodiments, provided herein are biofouling-resistant coatingscomprising charged or zwitterion compounds comprising phenyl-azidemoieties. In some instances, biofouling comprises microfouling ormacrofouling. Microfouling comprises formation of microorganism adhesion(e.g., bacteria adhesion) and/or biofilm. Biofilm is a group ofmicroorganism which adheres to a surface. In some instances, the adheredmicroorganisms are further embedded in a self-produced matrix ofextracellular polymeric substance, which comprises a polymericconglomeration of extracellular DNA, protein, and polysaccharides.Macrofouling comprises attachment of larger organisms.

Charged and/or zwitterionic compounds bind water molecules viaelectrostatically induced hydration. In such cases, charged and/orzwitterionic materials exhibit surface resistance toprotein/cell/bacterial adhesion, biofilm formation, and/or macrofouling.In some embodiments, the charged or zwitterion compounds comprisecopolymers. In some embodiments, also provided herein are methods ofmaking biofouling-resistant coatings comprising charged or zwitterioncopolymers via polymerization reaction. In some embodiments, thepolymerization reaction is addition polymerization, atomic transferradical polymerization (ATRP), coordination polymerization, free-radicalpolymerization, nitroxide-mediated radical polymerization (NMP),reversible addition-fragmentation chain-transfer polymerization (RAFT),or ring-opening metathesis polymerization (ROMP). In some embodiments,the ionic polymerization is anionic polymerization or cationicpolymerization. In some embodiments, the polymerization reaction isreversible-deactivation polymerization (RDP). In some embodiments, thepolymerization reaction is free-radical polymerization. In someembodiments, the polymerization reaction is atomic transfer radicalpolymerization (ATRP). In some embodiments, biofouling-resistantcoatings comprising charged or zwitterion copolymers are grafted onto apolymer surface of a device under a UV exposure. In some otherembodiments, charged or zwitterion copolymers are grafted onto asilicone-comprising surface of a device under a UV exposure. In someembodiments, charged or zwitterion copolymers are grafted onto a surfaceof a medical device under a UV exposure. In some other embodiments,charged or zwitterion copolymers are grafted onto a silicone-comprisingsurface of a medical device under a UV exposure. In some embodiments,charged or zwitterion are grafted onto a polymer surface of a medicaldevice under a UV exposure. In some other embodiments, charged orzwitterion copolymers are grafted onto a silicone-comprising polymersurface of a medical device under a UV exposure.

In some embodiments, a charged or zwitterion copolymer modified devicecomprises anti-fouling properties and is used to prevent and/or toreduce the development of biofouling. In some embodiments, a charged orzwitterion copolymer modified medical device comprises anti-foulingproperties and is used to prevent and/or to reduce the development ofbiofouling. In some embodiments, the charged or zwitterion coatingsprevent and/or reduce the attachment of microorganisms, plants, algae,or animals to a surface.

In additional embodiments, disclosed herein are compounds to be used toprepare charged or zwitterion copolymers of the disclosure as well asthe charged or zwitterion copolymers themselves to be used within themethods disclosed herein.

I. Compounds

In one aspect, described herein is a compound that has the structure ofFormula (I) or a salt or solvate thereof:

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—;    -   L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OR⁹,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O—, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and    -   R^(10b) is —(C═O)—C2-C6alkenyl, —(S═O)—C2-C6alkenyl, or        —(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has the structureselected from:

In some embodiments, the compound of Formula (I) has the followingstructure:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, Z is selected from —CR^(6a)R^(6b)—, —C(═O)—,—C(═NH)—, and —C(═NH)NR⁷—.

In some embodiments, Z is —CR^(6a)R^(6b)—. In some embodiments, Z is—C(═O)—. In some embodiments, Z is —C(═NH)—. In some embodiments, Z is—C(═NH)NR⁷—.

In some embodiments, each R³ is independently selected from hydrogen,optionally substituted C1-C4 alkyl, —X-optionally substituted C1-C4alkyl, optionally substituted aryl, and —X-optionally substituted aryl.In some embodiments, R³ is hydrogen. In some embodiments, R³ isoptionally substituted C1-C4 alkyl. In some embodiments, R³ is—X-optionally substituted C1-C4 alkyl. In some embodiments, R³ isoptionally substituted aryl. In some embodiments, R³ is —X— optionallysubstituted aryl.

In some embodiments, X is —C(═O)—, —S(═O)—, or —S(═O)₂—. In someembodiments, X is —C(═O)—. In some embodiments, X is —S(═O)—. In someembodiments, X is —S(═O)₂—.

In some embodiments, each R^(6a) and R^(6b) is hydrogen.

In some embodiments, m is 0, 1, 2, 3, 4, or 5. In some embodiments, m is0. In some embodiments, m is 1. In some embodiments, m is 2. In someembodiments, m is 3. In some embodiments, m is 4. In some embodiments, mis 5.

In some embodiments, R^(5a) is hydrogen; R^(5b) is —NR^(10a)R^(10b); andR^(5c) is hydrogen.

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ia):

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ib):

In some embodiments, R^(10a) is hydrogen, optionally substituted C1-C4alkyl, or optionally substituted aryl. In some embodiments, R^(10a) ishydrogen. In some embodiments, R^(10a) is optionally substituted C1-C4alkyl. In some embodiments, R^(10a) is CH₃. In some embodiments, R^(10a)is CH₂CH₃. In some embodiments, R^(10a) is optionally substituted aryl.In some embodiments, R^(10a) is phenyl.

In some embodiments, R^(10b) is —(C═O)—C2-C6alkenyl,—(S═O)—C2-C6alkenyl, or —(S═O)₂—C2-C6alkenyl. In some embodiments,R^(10b) is —(C═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has the structure of:

In another aspect, described herein is a compound that has the structureof Formula (II) or a salt or solvate thereof:

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C₁-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C₁-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹ and B² is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, B³ is —O—.

In some embodiments, D is —S(═O)₂OR^(9a) or —C(═O)OR^(9a). In someembodiments, D is —S(═O)₂OR^(9a). In some embodiments, D is—C(═O)OR^(9a).

In some embodiments, R^(9a) is hydrogen or —CH₃. In some embodiments,R^(9a) is hydrogen. In some embodiments, R^(9a) is —CH₃.

In some embodiments, D is —S(═O)₂O⁻ or —C(═O)O⁻. In some embodiments, Dis —S(═O)₂O⁻. In some embodiments, D is —C(═O)O⁻.

In some embodiments, each R^(6c) and R^(6d) is hydrogen.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

In some embodiments, n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is0. In some embodiments, n is 1. In some embodiments, m is 2. In someembodiments, n is 3. In some embodiments, n is 4. In some embodiments, nis 5.

In some embodiments, s is 1, 2, 3, or 4. In some embodiments, s is 1. Insome embodiments, s is 2. In some embodiments, s is 3. In someembodiments, s is 4.

In some embodiments, t is 1, 2, 3, or 4. In some embodiments, t is 1. Insome embodiments, t is 2. In some embodiments, t is 3. In someembodiments, t is 4.

In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. Insome embodiments, p is 2. In some embodiments, p is 3. In someembodiments, p is 4.

In some embodiments, q is 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55.In some embodiments, q is 45. In some embodiments, q is 46. In someembodiments, q is 47. In some embodiments, q is 48. In some embodiments,q is 49. In some embodiments, q is 50. In some embodiments, q is 51. Insome embodiments, q is 52. In some embodiments, q is 53. In someembodiments, q is 54. In some embodiments, q is 55.

In some embodiments, r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In someembodiments, r is 1. In some embodiments, r is 2. In some embodiments, ris 3. In some embodiments, r is 4. In some embodiments, r is 5. In someembodiments, r is 6. In some embodiments, r is 7. In some embodiments, ris 8. In some embodiments, r is 9. In some embodiments, r is 10.

In another aspect, described herein is a compound that has the structureof Formula (III) or a salt or solvate thereof:

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4e), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹, B², and B³ is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR⁹a

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+). In some embodiments,each R^(9a), R^(9b), or R^(9c) is independently H or —CH₃. In someembodiments, R^(9a) is H. In some embodiments, R^(9a) is —CH₃. In someembodiments, R^(9b) is H. In some embodiments, R^(9b) is —CH₃. In someembodiments, R^(9c) is H.

In some embodiments, R^(9c) is —CH₃.

In some embodiments, E is —S(═O)₂OR^(9a). In some embodiments, eachR^(9a) is H or —CH₃. In some embodiments, R^(9a) is H. In someembodiments, R^(9a) is —CH₃.

In some embodiments, each R^(6c) and R^(6d) is independently selectedfrom hydrogen and —CH₃.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(12a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

Any combination of the groups described above or below for the variousvariables is contemplated herein. Throughout the specification, groupsand substituents thereof are chosen by one skilled in the field toprovide stable moieties and compounds.

Further Forms of Compounds

In one aspect, the compound of Formula (I), (II) or (III), possesses oneor more stereocenters and each stereocenter exists independently ineither the R or S configuration. The compounds presented herein includeall diastereomeric, enantiomeric, and epimeric forms as well as theappropriate mixtures thereof. The compounds and methods provided hereininclude all cis, trans, syn, anti, entgegen (E), and zusammen (Z)isomers as well as the appropriate mixtures thereof. In certainembodiments, compounds described herein are prepared as their individualstereoisomers by reacting a racemic mixture of the compound with anoptically active resolving agent to form a pair of diastereoisomericcompounds/salts, separating the diastereomers and recovering theoptically pure enantiomers. In some embodiments, resolution ofenantiomers is carried out using covalent diastereomeric derivatives ofthe compounds described herein. In another embodiment, diastereomers areseparated by separation/resolution techniques based upon differences insolubility. In other embodiments, separation of stereoisomers isperformed by chromatography or by the forming diastereomeric salts andseparation by recrystallization, or chromatography, or any combinationthereof. Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers,Racemates and Resolutions”, John Wiley And Sons, Inc., 1981. In oneaspect, stereoisomers are obtained by stereoselective synthesis.

In another embodiment, the compounds described herein are labeledisotopically (e.g. with a radioisotope) or by another other means,including, but not limited to, the use of chromophores or fluorescentmoieties, bioluminescent labels, or chemiluminescent labels.

Compounds described herein include isotopically-labeled compounds, whichare identical to those recited in the various formulae and structurespresented herein, but for the fact that one or more atoms are replacedby an atom having an atomic mass or mass number different from theatomic mass or mass number usually found in nature. Examples of isotopesthat can be incorporated into the present compounds include isotopes ofhydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, suchas, for example, ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³⁵, ¹⁸F, ³⁶Cl. In oneaspect, isotopically-labeled compounds described herein, for examplethose into which radioactive isotopes such as ³H and ¹⁴C areincorporated, are useful in drug and/or substrate tissue distributionassays. In one aspect, substitution with isotopes such as deuteriumaffords certain therapeutic advantages resulting from greater metabolicstability, such as, for example, increased in vivo half-life or reduceddosage requirements.

Compounds described herein might be formed as, and/or used as, salts.The type of salts, include, but are not limited to: (1) acid additionsalts, formed by reacting the free base form of the compound with:inorganic acid, such as, for example, hydrochloric acid, hydrobromicacid, sulfuric acid, phosphoric acid, metaphosphoric acid, and the like;or with an organic acid, such as, for example, acetic acid, propionicacid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvicacid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid,fumaric acid, trifluoroacetic acid, tartaric acid, citric acid, benzoicacid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid,2-hydroxyethanesulfonic acid, benzenesulfonic acid, toluenesulfonicacid, 2-naphthalenesulfonic acid,4-methylbicyclo-[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid,4,4′-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionicacid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuricacid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylicacid, stearic acid, muconic acid, butyric acid, phenylacetic acid,phenylbutyric acid, valproic acid, and the like; (2) salts formed whenan acidic proton present in the parent compound is replaced by a metalion, e.g., an alkali metal ion (e.g. lithium, sodium, potassium), analkaline earth ion (e.g. magnesium, or calcium), or an aluminum ion. Insome cases, compounds described herein may coordinate with an organicbase, such as, but not limited to, ethanolamine, diethanolamine,triethanolamine, tromethamine, N-methylglucamine, dicyclohexylamine,tris(hydroxymethyl)methylamine. In other cases, compounds describedherein may form salts with amino acids such as, but not limited to,arginine, lysine, and the like. Acceptable inorganic bases used to formsalts with compounds that include an acidic proton, include, but are notlimited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide,sodium carbonate, sodium hydroxide, and the like.

It should be understood that a reference to a salt includes the solventaddition forms, particularly solvates. Solvates contain eitherstoichiometric or non-stoichiometric amounts of a solvent, such aswater, ethanol, and the like. Hydrates are formed when the solvent iswater, or alcoholates are formed when the solvent is alcohol. Solvatesof compounds described herein can be conveniently prepared or formedduring the processes described herein. In addition, the compoundsprovided herein can exist in unsolvated as well as solvated forms. Ingeneral, the solvated forms are considered equivalent to the unsolvatedforms for the purposes of the compounds and methods provided herein.

Synthesis of Compounds

Compounds described herein are synthesized using standard synthetictechniques or using methods known in the art in combination with methodsdescribed herein.

Unless otherwise indicated, conventional methods of mass spectroscopy,NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniquesand pharmacology are employed.

Compounds are prepared using standard organic chemistry techniques suchas those described in, for example, March's Advanced Organic Chemistry,6th Edition, John Wiley and Sons, Inc. Alternative reaction conditionsfor the synthetic transformations described herein may be employed suchas variation of solvent, reaction temperature, reaction time, as well asdifferent chemical reagents and other reaction conditions. The startingmaterials are available from commercial sources or are readily prepared.

Suitable reference books and treatise that detail the synthesis ofreactants useful in the preparation of compounds described herein, orprovide references to articles that describe the preparation, includefor example, “Synthetic Organic Chemistry”, John Wiley & Sons, Inc., NewYork; S. R. Sandler et al., “Organic Functional Group Preparations,” 2ndEd., Academic Press, New York, 1983; H. O. House, “Modem SyntheticReactions”, 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif. 1972; T. L.Gilchrist, “Heterocyclic Chemistry”, 2nd Ed., John Wiley & Sons, NewYork, 1992; J. March, “Advanced Organic Chemistry: Reactions, Mechanismsand Structure”, 4th Ed., Wiley Interscience, New York, 1992. Additionalsuitable reference books and treatise that detail the synthesis ofreactants useful in the preparation of compounds described herein, orprovide references to articles that describe the preparation, includefor example, Fuhrhop, J. and Penzlin G. “Organic Synthesis: Concepts,Methods, Starting Materials”, Second, Revised and Enlarged Edition(1994) John Wiley & Sons ISBN: 3 527-29074-5; Hoffman, R. V. “OrganicChemistry, An Intermediate Text” (1996) Oxford University Press, ISBN0-19-509618-5; Larock, R. C. “Comprehensive Organic Transformations: AGuide to Functional Group Preparations” 2nd Edition (1999) Wiley-VCH,ISBN: 0-471-19031-4; March, J. “Advanced Organic Chemistry: Reactions,Mechanisms, and Structure” 4th Edition (1992) John Wiley & Sons, ISBN:0-471-60180-2; Otera, J. (editor) “Modem Carbonyl Chemistry” (2000)Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. “Patai's 1992 Guide to theChemistry of Functional Groups” (1992) Interscience ISBN: 0-471-93022-9;Solomons, T. W. G. “Organic Chemistry” 7th Edition (2000) John Wiley &Sons, ISBN: 0-471-19095-0; Stowell, J. C., “Intermediate OrganicChemistry” 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471-57456-2;“Industrial Organic Chemicals: Starting Materials and Intermediates: AnUllmann's Encyclopedia” (1999) John Wiley & Sons, ISBN: 3-527-29645-X,in 8 volumes; “Organic Reactions” (1942-2000) John Wiley & Sons, in over55 volumes; and “Chemistry of Functional Groups” John Wiley & Sons, in73 volumes.

In the reactions described, it may be necessary to protect reactivefunctional groups, for example hydroxy, amino, imino, thio or carboxygroups, where these are desired in the final product, in order to avoidtheir unwanted participation in reactions. A detailed description oftechniques applicable to the creation of protecting groups and theirremoval are described in Greene and Wuts, Protective Groups in OrganicSynthesis, 3rd Ed., John Wiley & Sons, New York, N.Y., 1999, andKocienski, Protective Groups, Thieme Verlag, New York, N.Y., 1994, whichare incorporated herein by reference for such disclosure).

In some embodiments, compounds are synthesized as described in theExamples section.

II. Biofouling-Resistant Coatings

In one aspect, described herein is a biofouling-resistant coatingcomprising a compound of Formula (I):

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—;    -   L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OR⁹,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O—, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and    -   R^(10b) is —(C═O)—C2-C6alkenyl, —(S═O)—C2-C6alkenyl, or        —(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has the structureselected from:

In some embodiments, the compound of Formula (I) has the followingstructure:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, Z is selected from —CR^(6a)R^(6b)—, —C(═O)—,—C(═NH)—, and —C(═NH)NR⁷—.

In some embodiments, Z is —CR^(6a)R^(6b)—. In some embodiments, Z is—C(═O)—. In some embodiments, Z is —C(═NH)—. In some embodiments, Z is—C(═NH)NR⁷—.

In some embodiments, each R³ is independently selected from hydrogen,optionally substituted C1-C4 alkyl, —X-optionally substituted C1-C4alkyl, optionally substituted aryl, and —X-optionally substituted aryl.In some embodiments, R³ is hydrogen. In some embodiments, R³ isoptionally substituted C1-C4 alkyl. In some embodiments, R³ is—X-optionally substituted C1-C4 alkyl. In some embodiments, R³ isoptionally substituted aryl. In some embodiments, R³ is —X-optionallysubstituted aryl.

In some embodiments, X is —C(═O)—, —S(═O)—, or —S(═O)₂—. In someembodiments, X is —C(═O)—. In some embodiments, X is —S(═O)—. In someembodiments, X is —S(═O)₂—.

In some embodiments, each R^(6a) and R^(6b) is hydrogen.

In some embodiments, m is 0, 1, 2, 3, 4, or 5. In some embodiments, m is0. In some embodiments, m is 1. In some embodiments, m is 2. In someembodiments, m is 3. In some embodiments, m is 4. In some embodiments, mis 5.

In some embodiments, R^(5a) is hydrogen; R^(5b) is —NR^(10a)R^(10b); andR^(5c) is hydrogen.

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ia):

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ib):

In some embodiments, R^(10a) is hydrogen, optionally substituted C1-C4alkyl, or optionally substituted aryl. In some embodiments, R^(10a) ishydrogen. In some embodiments, R^(10a) is optionally substituted C1-C4alkyl. In some embodiments, R^(10a) is CH₃. In some embodiments, R^(10a)is CH₂CH₃. In some embodiments, R^(10a) is optionally substituted aryl.In some embodiments, R^(10a) is phenyl.

In some embodiments, R^(10b) is —(C═O)—C2-C6alkenyl,—(S═O)—C2-C6alkenyl, or —(S═O)₂—C2-C6alkenyl. In some embodiments,R^(10b) is —(C═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)₂—C2-C6alkenyl.

In another aspect, described herein is a biofouling-resistant coatingcomprising a compound of Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹ and B² is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, B³ is —O—.

In some embodiments, D is —S(═O)₂OR^(9a) or —C(═O)OR^(9a). In someembodiments, D is —S(═O)₂OR^(9a). In some embodiments, D is—C(═O)OR^(9a).

In some embodiments, R^(9a) is hydrogen or —CH₃. In some embodiments,R^(9a) is hydrogen. In some embodiments, R^(9a) is —CH₃.

In some embodiments, D is —S(═O)₂O⁻ or —C(═O)O⁻. In some embodiments, Dis —S(═O)₂O⁻.

In some embodiments, D is —C(═O)O⁻.

In some embodiments, each R^(6c) and R^(6d) is hydrogen.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

In some embodiments, n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is0. In some embodiments, n is 1. In some embodiments, m is 2. In someembodiments, n is 3. In some embodiments, n is 4. In some embodiments, nis 5.

In some embodiments, s is 1, 2, 3, or 4. In some embodiments, s is 1. Insome embodiments, s is 2. In some embodiments, s is 3. In someembodiments, s is 4.

In some embodiments, t is 1, 2, 3, or 4. In some embodiments, t is 1. Insome embodiments, t is 2. In some embodiments, t is 3. In someembodiments, t is 4.

In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. Insome embodiments, p is 2. In some embodiments, p is 3. In someembodiments, p is 4.

In some embodiments, q is 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55.In some embodiments, q is 45. In some embodiments, q is 46. In someembodiments, q is 47. In some embodiments, q is 48. In some embodiments,q is 49. In some embodiments, q is 50. In some embodiments, q is 51. Insome embodiments, q is 52. In some embodiments, q is 53. In someembodiments, q is 54. In some embodiments, q is 55.

In some embodiments, r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In someembodiments, r is 1. In some embodiments, r is 2. In some embodiments, ris 3. In some embodiments, r is 4. In some embodiments, r is 5. In someembodiments, r is 6. In some embodiments, r is 7. In some embodiments, ris 8. In some embodiments, r is 9. In some embodiments, r is 10.

In another aspect, described herein is a biofouling-resistant coatingcomprising a compound of Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹, B², and B³ is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR^(9a).

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+). In some embodiments,each R^(9a), R^(9b), or R^(9c) is independently H or —CH₃. In someembodiments, R^(9a) is H. In some embodiments, R^(9a) is —CH₃. In someembodiments, R^(9b) is H. In some embodiments, R^(9b) is —CH₃. In someembodiments, R^(9c) is H.

In some embodiments, R^(9c) is —CH₃.

In some embodiments, E is —S(═O)₂OR^(9a). In some embodiments, eachR^(9a) is H or —CH₃. In some embodiments, R^(9a) is H. In someembodiments, R^(9a) is —CH₃.

In some embodiments, each R^(6c) and R^(6d) is independently selectedfrom hydrogen and —CH₃.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(12a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

Any combination of the groups described above or below for the variousvariables is contemplated herein. Throughout the specification, groupsand substituents thereof are chosen by one skilled in the field toprovide stable moieties and compounds.

In some embodiments, the biofouling-resistant coating described hereincomprises one or more compounds of Formula (I), (II), or (III).

In some embodiments, the biofouling-resistant coating described hereincomprises one or more copolymers of Formula (II) or (III).

In some embodiments, the biofouling-resistant coating comprising one ormore compounds of Formula (I), (II), and (III) is applied onto a surfaceof the device. In some embodiments, the surface of the device comprisesa polymer. In some embodiments, the polymer is selected frompolysiloxanes, polyurethanes, polyamides, polyimides, epoxy resins,polyesters, polyolefins, polysulfones, polycarbonates,polyvinylchloride, polyvinylidene difluoride, polyethers, polyetherterpthalate, or a mixture thereof.

II. Devices

In certain embodiments, provided herein are devices coated by one ormore compounds described herein. In some instances, provided herein aremedical devices coated by one or more compounds described herein. Inother instances, provided herein are non-medical devices coated by oneor more compounds described herein. In additional instances, providedherein are devices coated by one or more compounds described herein inwhich the coated device reduces the potential for infection.

In some embodiments, the device comprises a polymer-based device. Insome embodiments, the polymer-based device comprises a polyolefinicdevice. In some embodiments, the polyolefinic device comprises a devicemodified with polyethylene (PE), polypropylene (PP), polyamide (PA),polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVdF),polyvinyl chloride (PVC), or a combination thereof. In some embodiments,the device comprises a microporous device or a nonwoven device. In someembodiments, the device comprises a carbon-based device comprising amoiety capable of binding with a compound that has a structure ofFormula (I), (II), or (III). In some embodiments, the carbon-baseddevice comprises a polymer moiety. In some embodiments, the carbon-baseddevice comprises a carbon-based polymer. In some embodiments, thecarbon-based device comprises a polyolefin moiety. In some embodiments,the polyolefin moiety comprises a polyethylene (PE) moiety, apolypropylene (PP) moiety, a polyamide (PA) moiety, apolytetrafluoroethylene (PTFE) moiety, a polyvinylidene fluoride (PVdF)moiety, or a polyvinyl chloride (PVC) moiety.

In some embodiments, the device comprises a carbon-based device. In someembodiments, the carbon-based device comprises a carbon-based polymer.In some embodiments, the carbon-based device comprises a polyolefinmoiety. In some embodiments, the polyolefin moiety comprisespolyethylene moiety, polypropylene moiety, polyvinyl chloride moiety,polyvinylidene fluoride moiety, polytetrafluoroethylene moiety,polychlorotrifluoroethylene moiety, or polystyrene moiety.

In some embodiments, the carbon-based polymer comprises polyamidemoiety, polyurethane moiety, phenol-formaldehyde resin moiety,polycarbonate moiety, polychloroprene moiety, polyacrylonitrile moiety,polimide moiety, or polyester moiety. In some embodiments, thecarbon-based polymer comprises nylon. In some embodiments, thecarbon-based polymer comprises polyethylene terephthalate.

In some embodiments, the device comprises a silicon-based device. Insome embodiments, the silicon-based device comprises a silicon-basedpolymer moiety. In some embodiments, the device comprises asilicon-based device comprising a moiety capable of binding with acompound that has a structure of Formula (I), (II), or (III). In someembodiments, the silicon-based device comprises a polymer moiety. Insome embodiments, the silicon-based device comprises a siloxane polymermoiety, a sesquisiloxane polymer moiety, a siloxane-silarylene polymermoiety, a silalkylene polymer moiety, a polysilane moiety, apolysilylene moiety, or a polysilazane moiety.

In some embodiments, the silicon-based device comprises a siloxanepolymer moiety. In some embodiments, the silicon-based device comprisessilicone polymer. In some embodiments, the silicon-based devicecomprises a silicone-based device.

In some embodiments, the device comprises a carbon-based device or asilicon-based device.

In some embodiments, a device described herein coated by a compounddescribed herein leads to a reduced potential for infection relative toa device not coated by the compound. In some instances, the reducedpotential for infection is by about 10%, 20%, 30%, 40%, 50%, 60%, 70%,80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to a device notcoated by the compound. In some instances, the reduced potential forinfection is by about 10%, or more relative to a device not coated bythe compound. In some instances, the reduced potential for infection isby about 20%, or more relative to a device not coated by the compound.In some instances, the reduced potential for infection is by about 30%,or more relative to a device not coated by the compound. In someinstances, the reduced potential for infection is by about 40%, or morerelative to a device not coated by the compound. In some instances, thereduced potential for infection is by about 50%, or more relative to adevice not coated by the compound. In some instances, the reducedpotential for infection is by about 60%, or more relative to a devicenot coated by the compound. In some instances, the reduced potential forinfection is by about 70%, or more relative to a device not coated bythe compound. In some instances, the reduced potential for infection isby about 80%, or more relative to a device not coated by the compound.In some instances, the reduced potential for infection is by about 90%,or more relative to a device not coated by the compound. In someinstances, the reduced potential for infection is by about 95%, or morerelative to a device not coated by the compound. In some instances, thereduced potential for infection is by about 99%, or more relative to adevice not coated by the compound. In some instances, the reducedpotential for infection is by about 99.5%, or more relative to a devicenot coated by the compound. In some instances, the reduced potential forinfection is by about 99.9%, or more relative to a device not coated bythe compound.

Medical Devices

In some embodiments, a device described herein is a medical device. Insome cases, a medical device described herein comprises a dentalinstrument or a medical instrument. In some instances, a medical devicecomprises an implant, an IV, a prosthesis, a suturing material, a valve,a stent, a catheter, a rod, a shunt, a scope, a contact lens, a tubing,a wiring, an electrode, a clip, a fastener, a syringe, a container, or acombination thereof. In some embodiments, a medical device comprises animplant. In some embodiments, a medical device comprises an IV. In someembodiments, a medical device comprises a prosthesis. In someembodiments, a medical device comprises a suturing material. In someembodiments, a medical device comprises a valve. In some embodiments, amedical device comprises a stent. In some embodiments, a medical devicecomprises a catheter. In some embodiments, a medical device comprises arod. In some embodiments, a medical device comprises a shunt. In someembodiments, a medical device comprises a scope. In some embodiments, amedical device comprises a contact lens. In some embodiments, a medicaldevice comprises a tubing. In some embodiments, a medical devicecomprises a wiring. In some embodiments, a medical device comprises anelectrode. In some embodiments, a medical device comprises a clip. Insome embodiments, a medical device comprises a fastener. In someembodiments, a medical device comprises a syringe. In some embodiments,a medical device comprises a container. In some instances, a devicedescribed herein comprises a dental instrument or a medical instrument.In some instances, a device described herein comprises an implant, anIV, a prosthesis, a suturing material, a valve, a stent, a catheter, arod, a shunt, a scope, a contact lens, a tubing, a wiring, an electrode,a clip, a fastener, a syringe, a container, or a combination thereof. Insome embodiments, a device comprises an implant. In some embodiments, adevice comprises an IV. In some embodiments, a device comprises aprosthesis. In some embodiments, a device comprises a suturing material.In some embodiments, a device comprises a valve. In some embodiments, adevice comprises a stent. In some embodiments, a device comprises acatheter. In some embodiments, a device comprises a rod. In someembodiments, a device comprises a shunt. In some embodiments, a devicecomprises a scope. In some embodiments, a device comprises a contactlens. In some embodiments, a device comprises a tubing. In someembodiments, a device comprises a wiring. In some embodiments, a devicecomprises an electrode. In some embodiments, a device comprises a clip.In some embodiments, a device comprises a fastener. In some embodiments,a device comprises a syringe. In some embodiments, a device comprises acontainer.

In some embodiments, a compound described herein is coated onto amedical device. In some instances, a compound described herein is coatedonto a medical device to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto a dental instrument or amedical instrument to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto an implant, an IV, aprosthesis, a suturing material, a valve, a stent, a catheter, a rod, ashunt, a scope, a contact lens, a tubing, a wiring, an electrode, aclip, a fastener, a syringe, a container, or a combination thereof toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm).

In some cases, a device described herein comprises a catheter. In somecases, a catheter comprises an indwelling catheter. In some instances, acatheter comprises a permcath. In some instances, a catheter comprises auretic catheter or a Foley catheter.

In some instances, a compound described herein is coated onto a catheterto prevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto an indwelling catheter to prevent and/or reduce biofouling(e.g., microfouling such as bacteria adhesion or biofilm). In someinstances, a compound described herein is coated onto a permcath toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto a uretic catheter to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto a Foley catheter to preventand/or reduce biofouling (e.g., microfouling such as bacteria adhesionor biofilm).

In some instances, a device described herein comprises an implant. Insome instances, an implant comprises a dental implant or an orthopedicimplant. In some cases, a device described herein comprises a dentalimplant. In other cases, a device described herein comprises anorthopedic implant.

In some instances, a compound described herein is coated onto an implantto prevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto a dental implant to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto an orthopedic implant toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm).

In some embodiments, a device described herein comprises an IV. In someinstances, a compound described herein is coated onto an IV to preventand/or reduce biofouling (e.g., microfouling such as bacteria adhesionor biofilm).

In some embodiments, a device described herein comprises a prosthesis.In some cases, a prosthesis comprises an artificial bone, an artificialjoint, an artificial organ, or a denture. In some cases, an artificialorgan comprises an artificial pancreas, an artificial heart, anartificial limb, or a heart valve. In some embodiments, a devicedescribed herein comprises an artificial bone, an artificial joint, anartificial organ or a denture. In some embodiments, a device describedherein comprises an artificial pancreas, an artificial heart, anartificial limb, or a heart valve.

In some instances, a compound described herein is coated onto prosthesisto prevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto an artificial bone, an artificial joint, an artificialorgan, or a denture to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto an artificial pancreas, anartificial heart, an artificial limb, or a heart valve to prevent and/orreduce biofouling (e.g., microfouling such as bacteria adhesion orbiofilm).

In some embodiments, a device described herein comprises a stent. Insome instances, a stent is a small expandable tube used to thepassageway of a blood vessel or duct remains open. In some cases, astent comprises a coronary stent, a vascular stent, or a biliary stent.In some instances, a coronary stent is also referred to as a cardiacstent or a heart stent. In some embodiments, a device described hereincomprises a coronary stent, a vascular stent, or a biliary stent.

In some instances, a compound described herein is coated onto stent toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto a coronary stent, a vascular stent, or a biliary stent toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm).

In some instances, a device described herein comprises shunt. In someinstances, a shunt is a hole or a small passage which allows fluidmovement from one part of a body to another. In some instances, a shuntdiffers from a stent in that a shunt connects two previously unconnectedportions.

In some instances, a shunt is an acquired shunt. In some cases, a shuntcomprises a cardiac shunt, a cerebral shunt, a lumbar-peritoneal shunt,a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt (PSS),a portacaval shunt, or a vesico-amniotic shunt. In some cases, a cardiacshunt comprises a right-to-left, left-to-right, or bidirectional shunt.In some cases, a cerebral shunt comprises drainage of excesscerebrospinal fluid from the brain into the chest or abdomen cavity. Insome cases, a lumbar-peritoneal shunt comprises channeling cerebrospinalfluid from the lumbar thecal sac into the peritoneal cavity. In someinstances, a peritoneovenous shunt (also referred to as Denver shunt)drains peritoneal fluid from the peritoneum into the veins. In somecases, a portosystemic shunt (PSS) is a liver shunt which allows bypassof the liver by the circulatory system. In some cases, a portacavalshunt connects the portal vein with the inferior vena cava, fortreatment of high blood pressure in the liver. In some cases, avesico-amniotic shunt is for drainage of excess fluid in a fetus bladderinto the surrounding area. In some cases, a device described hereincomprises a cardiac shunt, a cerebral shunt, a lumbar-peritoneal shunt,a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt (PSS),a portacaval shunt, or a vesico-amniotic shunt.

In some instances, a compound described herein is coated onto shunt toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto a cardiac shunt, a cerebral shunt, a lumbar-peritonealshunt, a peritoneovenous shunt, a pulmonary shunt, a portosystemic shunt(PSS), a portacaval shunt, or a vesico-amniotic shunt to prevent and/orreduce biofouling (e.g., microfouling such as bacteria adhesion orbiofilm).

In some instances, a device described herein comprises a scope. In somecases, a scope is a medical instrument used in an image-guided surgery.In some cases, a scope comprises endoscope or laparoscope. Endoscopy isa medical procedure for examining the GI tract with the aid of anendoscope. In some cases, endoscopy further comprises sigmoidoscopy andcolonoscopy.

Laparoscopy is a diagnostic procedure for examining internal organsutilizing a laparoscope. In some instances, a device described hereincomprises a scope used in endoscopy. In other instances, a devicedescribed herein comprises a scope used in laparoscopy.

In some instances, a compound described herein is coated onto scope toprevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto endoscope to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm). In some instances, acompound described herein is coated onto laparoscope to prevent and/orreduce biofouling (e.g., microfouling such as bacteria adhesion orbiofilm).

In some embodiments, a device described herein comprises suturingmaterial, valve, rod, tubing, wiring, electrode, clip, fastener, or acombination thereof. In some instances, a compound described herein iscoated onto suturing material, valve, rod, tubing, wiring, electrode,clip, fastener, or a combination thereof to prevent and/or reducebiofouling (e.g., microfouling such as bacteria adhesion or biofilm).

In some embodiments, a device described herein comprises a syringe. Insome cases, a syringe further comprises a needle. In some instances, acompound described herein is coated onto a syringe to prevent and/orreduce biofouling (e.g., microfouling such as bacteria adhesion orbiofilm).

In some embodiments, a device described herein comprises a container,such as for storage of one or more medical devices. In some instances, acompound described herein is coated onto a container to prevent and/orreduce biofouling (e.g., microfouling such as bacteria adhesion orbiofilm).

In some embodiments, a device described herein comprises a bandage or apatch. In some cases, a device described herein comprises a bandage. Inother cases, a device described herein comprises a patch.

In some instances, a compound described herein is coated onto a bandageto prevent and/or reduce biofouling (e.g., microfouling such as bacteriaadhesion or biofilm). In some instances, a compound described herein iscoated onto patch to prevent and/or reduce biofouling (e.g.,microfouling such as bacteria adhesion or biofilm).

In some embodiments, a compound described above is a compound that has astructure represented by a Formula (I):

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—; L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OR⁹,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O—, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and    -   R^(10b) is —(C═O)—C2-C6alkenyl, —(S═O)—C2-C6alkenyl, or        —(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has the structureselected from:

In some embodiments, the compound of Formula (I) has the followingstructure:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, Z is selected from —CR^(6a)R^(6b)—, —C(═O)—,—C(═NH)—, and —C(═NH)NR⁷—.

In some embodiments, Z is —CR^(6a)R^(6b)—. In some embodiments, Z is—C(═O)—. In some embodiments, Z is —C(═NH)—. In some embodiments, Z is—C(═NH)NR⁷—.

In some embodiments, each R³ is independently selected from hydrogen,optionally substituted C1-C4 alkyl, —X-optionally substituted C1-C4alkyl, optionally substituted aryl, and —X-optionally substituted aryl.In some embodiments, R³ is hydrogen. In some embodiments, R³ isoptionally substituted C1-C4 alkyl. In some embodiments, R³ is—X-optionally substituted C1-C4 alkyl. In some embodiments, R³ isoptionally substituted aryl. In some embodiments, R³ is —X-optionallysubstituted aryl.

In some embodiments, X is —C(═O)—, —S(═O)—, or —S(═O)₂—. In someembodiments, X is —C(═O)—. In some embodiments, X is —S(═O)—. In someembodiments, X is —S(═O)₂—.

In some embodiments, each R^(6a) and R^(6b) is hydrogen.

In some embodiments, m is 0, 1, 2, 3, 4, or 5. In some embodiments, m is0. In some embodiments, m is 1. In some embodiments, m is 2. In someembodiments, m is 3. In some embodiments, m is 4. In some embodiments, mis 5.

In some embodiments, R^(5a) is hydrogen; R^(5b) is —NR^(10a)R^(10b); andR^(5c) is hydrogen.

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ia):

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ib):

In some embodiments, R^(10a) is hydrogen, optionally substituted C1-C4alkyl, or optionally substituted aryl. In some embodiments, R^(10a) ishydrogen. In some embodiments, R^(10a) is optionally substituted C1-C4alkyl. In some embodiments, R^(10a) is CH₃. In some embodiments, R^(10a)is CH₂CH₃. In some embodiments, R^(10a) is optionally substituted aryl.In some embodiments, R^(10a) is phenyl.

In some embodiments, R^(10b) is —(C═O)—C2-C6alkenyl,—(S═O)—C2-C6alkenyl, or —(S═O)₂—C2-C6alkenyl. In some embodiments,R^(10b) is —(C═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)₂—C2-C6alkenyl.

In some embodiments, a compound described above is a compound that has astructure represented by a Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹ and B² is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, B³ is —O—.

In some embodiments, D is —S(═O)₂OR^(9a) or —C(═O)OR^(9a). In someembodiments, D is —S(═O)₂OR^(9a). In some embodiments, D is—C(═O)OR^(9a).

In some embodiments, R^(9a) is hydrogen or —CH₃. In some embodiments,R^(9a) is hydrogen. In some embodiments, R^(9a) is —CH₃.

In some embodiments, D is —S(═O)₂O⁻ or —C(═O)O⁻. In some embodiments, Dis —S(═O)₂O⁻.

In some embodiments, D is —C(═O)O⁻.

In some embodiments, each R^(6c) and R^(6d) is hydrogen.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

In some embodiments, n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is0. In some embodiments, n is 1. In some embodiments, m is 2. In someembodiments, n is 3. In some embodiments, n is 4. In some embodiments, nis 5.

In some embodiments, s is 1, 2, 3, or 4. In some embodiments, s is 1. Insome embodiments, s is 2. In some embodiments, s is 3. In someembodiments, s is 4.

In some embodiments, t is 1, 2, 3, or 4. In some embodiments, t is 1. Insome embodiments, t is 2. In some embodiments, t is 3. In someembodiments, t is 4.

In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. Insome embodiments, p is 2. In some embodiments, p is 3. In someembodiments, p is 4.

In some embodiments, q is 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55.In some embodiments, q is 45. In some embodiments, q is 46. In someembodiments, q is 47. In some embodiments, q is 48. In some embodiments,q is 49. In some embodiments, q is 50. In some embodiments, q is 51. Insome embodiments, q is 52. In some embodiments, q is 53. In someembodiments, q is 54. In some embodiments, q is 55.

In some embodiments, r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In someembodiments, r is 1. In some embodiments, r is 2. In some embodiments, ris 3. In some embodiments, r is 4. In some embodiments, r is 5. In someembodiments, r is 6. In some embodiments, r is 7. In some embodiments, ris 8. In some embodiments, r is 9. In some embodiments, r is 10.

In some embodiments, a compound described above is a compound that has astructure represented by a Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹, B², and B³ is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR^(9a).

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+). In some embodiments,each R^(9a), R^(9b), or R^(9c) is independently H or —CH₃. In someembodiments, R^(9a) is H. In some embodiments, R^(9a) is —CH₃. In someembodiments, R^(9b) is H. In some embodiments, R^(9b) is —CH₃. In someembodiments, R^(9c) is H. In some embodiments, R^(9c) is —CH₃.

In some embodiments, E is —S(═O)₂OR^(9a). In some embodiments, eachR^(9a) is H or —CH₃. In some embodiments, R^(9a) is H. In someembodiments, R^(9a) is —CH₃.

In some embodiments, each R^(6c) and R^(6d) is independently selectedfrom hydrogen and —CH₃.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(12a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

Biofouling-Resistant Medical Devices

In some embodiments, disclosed herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with one ormore compounds of Formula (I), (II), or (III) described herein having anumber-average molecular weight of between about 10,000 and about250,000.

In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of at least about 10,000, about 20,000,about 30,000, about 40,000, about 50,000, about 60,000, about 70,000,about 80,000, about 90,000, about 100,000, about 110,000, about 120,000,about 130,000, about 140,000, about 150,000, about 160,000, about170,000, about 180,000, about 190,000, or about 200,000. In someembodiments, the phenyl azide-based copolymer has a number-averagemolecular weight of no more than about 10,000, about 20,000, about30,000, about 40,000, about 50,000, about 60,000, about 70,000, about80,000, about 90,000, about 100,000, about 110,000, about 120,000, about130,000, about 140,000, about 150,000, about 160,000, about 170,000,about 180,000, about 190,000, or about 200,000.

In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about40,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about60,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about80,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about100,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 10,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about40,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about60,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about80,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about100,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about60,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about80,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about100,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 40,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about80,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about100,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 60,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about100,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 80,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 100,000 and about120,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 100,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 100,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 100,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 100,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 120,000 and about140,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 120,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 120,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 120,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 140,000 and about160,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 140,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 140,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 160,000 and about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 160,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 200,000 and about250,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of about 10,000. In some embodiments,the phenyl azide-based copolymer has a number-average molecular weightof about 20,000. In some embodiments, the phenyl azide-based copolymerhas a number-average molecular weight of about 40,000. In someembodiments, the phenyl azide-based copolymer has a number-averagemolecular weight of about 60,000. In some embodiments, the phenylazide-based copolymer has a number-average molecular weight of about80,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of about 100,000. In some embodiments,the phenyl azide-based copolymer has a number-average molecular weightof about 120,000. In some embodiments, the phenyl azide-based copolymerhas a number-average molecular weight of about 140,000. In someembodiments, the phenyl azide-based copolymer has a number-averagemolecular weight of about 160,000. In some embodiments, the phenylazide-based copolymer has a number-average molecular weight of about200,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of about 250,000.

In some embodiments, disclosed herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with one ormore compounds of Formula (I), (II), or (III) described herein having anumber-average molecular weight of between about 14,000 and about21,000.

In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about15,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about16,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about17,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about18,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about19,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 14,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about16,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about17,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about18,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about19,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 15,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 16,000 and about17,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 16,000 and about18,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 16,000 and about19,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 16,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 16,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 17,000 and about18,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 17,000 and about19,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 17,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 17,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 18,000 and about19,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 18,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 18,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 19,000 and about20,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 19,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of between about 20,000 and about21,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of about 14,000. In some embodiments,the phenyl azide-based copolymer has a number-average molecular weightof about 15,000. In some embodiments, the phenyl azide-based copolymerhas a number-average molecular weight of about 16,000. In someembodiments, the phenyl azide-based copolymer has a number-averagemolecular weight of about 17,000. In some embodiments, the phenylazide-based copolymer has a number-average molecular weight of about18,000. In some embodiments, the phenyl azide-based copolymer has anumber-average molecular weight of about 19,000. In some embodiments,the phenyl azide-based copolymer has a number-average molecular weightof about 20,000. In some embodiments, the phenyl azide-based copolymerhas a number-average molecular weight of about 21,000.

In some embodiments, disclosed herein is a biofouling-resistant medicaldevice, wherein a surface of the medical device is coated with one ormore compounds of Formula (I), (II), or (III) described herein having apolydispersity index (PDI) of between about 1 and 1.5.

In some embodiments, the surface of the medical device is coated with aphenyl azide-based copolymer having a polydispersity index (PDI) of atleast about 1, about 1.1, about 1.2, about 1.3, about 1.4, or about 1.5.In some embodiments, the surface of the medical device is coated with aphenyl azide-based copolymer having a polydispersity index (PDI) of nomore than about 1, about 1.1, about 1.2, about 1.3, about 1.4, or about1.5.

In some embodiments, the surface of the medical device is coated with aphenyl azide-based copolymer having a polydispersity index (PDI) ofbetween about 1 and 1.1. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1 and 1.2. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1 and 1.3. In some embodiments, the surface of the medical deviceis coated with a phenyl azide-based copolymer having a polydispersityindex (PDI) of between about 1 and 1.4. In some embodiments, the surfaceof the medical device is coated with a phenyl azide-based copolymerhaving a polydispersity index (PDI) of between about 1 and 1.5. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1.1 and 1.2. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1.1 and 1.3. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1.1 and 1.4. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1.1 and 1.5. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1.2 and 1.3. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1.2 and 1.4. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1.2 and 1.5. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1.3 and 1.4. In someembodiments, the surface of the medical device is coated with a phenylazide-based copolymer having a polydispersity index (PDI) of betweenabout 1.3 and 1.5. In some embodiments, the surface of the medicaldevice is coated with a phenyl azide-based copolymer having apolydispersity index (PDI) of between about 1.4 and 1.5. In someembodiments, the PDI is about 1. In some embodiments, the PDI is about1.1. In some embodiments, the PDI is about 1.2. In some embodiments, thePDI is about 1.3. In some embodiments, the PDI is about 1.4. In someembodiments, the PDI is about 1.5.

In some embodiments, the PDI is about 1.11. In some embodiments, the PDIis about 1.12. In some embodiments, the PDI is about 1.13. In someembodiments, the PDI is about 1.14. In some embodiments, the PDI isabout 1.15. In some embodiments, the PDI is about 1.16. In someembodiments, the PDI is about 1.17. In some embodiments, the PDI isabout 1.18. In some embodiments, the PDI is about 1.19. In someembodiments, the PDI is about 1.21. In some embodiments, the PDI isabout 1.22. In some embodiments, the PDI is about 1.23. In someembodiments, the PDI is about 1.24. In some embodiments, the PDI isabout 1.25.

In some embodiments, the medical device comprises a dental instrument ora medical instrument. In some embodiments, the medical device comprisesan implant, an IV, a prosthesis, a suturing material, a valve, a stent,a catheter, a rod, a shunt, a scope, a contact lens, a tubing, a wiring,an electrode, a clip, a fastener, a syringe, a container, or acombination thereof. In some embodiments, the medical device is acontact lens. In some embodiments, the medical device is a catheter. Insome embodiments, the catheter is an indwelling catheter. In someembodiments, the catheter comprises a uretic catheter or a Foleycatheter. In some embodiments, the medical device is a scope. In someembodiments, the scope comprises a scope utilized in an image-guidedsurgery. In some embodiments, the scope comprises a scope utilized inendoscopy or laparoscopy.

In some embodiments, the medical device comprises auditory prostheses,artificial larynx, dental implants, mammary implants, penile implants,cranio/facial tendons, tendons, ligaments, menisci, or disks. In someembodiments, the medical device comprises artificial bones, artificialjoints, or artificial organs. In some embodiments, the artificial organscomprise artificial pancreas, artificial hearts, artificial limbs, orheart valves. In some embodiments, the medical device comprises abandage or a patch.

In some embodiments, the copolymer comprises zwitterionic copolymer. Insome embodiments, the zwitterionic copolymer comprises polysulfobetaine.

In some embodiments, the biofouling is produced by a bacterium, a virus,and/or a fungus.

Non-Medical Devices

In some embodiments, a device described herein comprises a non-medicaldevice. In some instances, a non-medical device comprises a marinevessel or an underwater construction. In some cases, a surface of anon-medical device for coating a compound described herein comprises asurface that is immersed in water. In some cases, the immersion is animmersion of at least 30 minutes, 1 hour, 6 hours, 12 hours, 1 day, 2days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days,11 days, 12 days, 13 days, 14 days, 15 days, 30 days, 1 month, 2 months,3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10months, 11 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years,or more.

In some instances, a device described herein comprises a marine vessel.In some instances, a surface of a marine vessel comprises a surface thatis immersed in water. In some cases, a surface of a marine vesselcomprises a surface that is immersed in water for at least 30 minutes, 1hour, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days,7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2years, 3 years, 4 years, 5 years, 10 years, or more. In some instances,the surface of a device for coating a compound described hereincomprises the hull of a marine vessel.

In some instances, a device described herein comprises an underwaterconstruction. In some instances, an underwater construction comprises anunderwater cable, a current measurement instrument, or an offshore oilplatform. In some cases, a device described herein comprises anunderwater cable. In some cases, a device described herein comprises acurrent measurement instrument. In other cases, a device describedherein comprises an offshore oil platform.

In some cases, an underwater construction is a construction in which theconstruction is immersed in water for at least 30 minutes, 1 hour, 6hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days,8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 30days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3years, 4 years, 5 years, or more. In some cases, a surface of anunderwater construction is a construction in which the surface isimmersed in water for at least 30 minutes, 1 hour, 6 hours, 12 hours, 1day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10days, 11 days, 12 days, 13 days, 14 days, 15 days, 30 days, 1 month, 2months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, 5years, 10 years, or more. In some instances, a device described hereincomprises an underwater construction in which the surface is immersed inwater for at least 30 minutes, 1 hour, 6 hours, 12 hours, 1 day, 2 days,3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11days, 12 days, 13 days, 14 days, 15 days, 30 days, 1 month, 2 months, 3months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10months, 11 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years,or more.

In some embodiments, a compound described herein is coated onto a device(e.g., a medical device or a non-medical device). In some cases, acompound described herein is coated directly onto a device (e.g., amedical device or a non-medical device). In other instances, a compounddescribed herein is coated indirectly onto a device (e.g., a medicaldevice or a non-medical device). In some cases, the coating comprisesdip-coating. In other cases, the coating comprises spray coating.

In some embodiments, a compound described herein is coated onto a device(e.g., a medical device or a non-medical device) to reduce the formationof biofouling. In some cases, the formation of biofouling is reduced byabout 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%,99.9%, or more relative to a device not coated with the compound. Insome instances, the formation of biofouling is reduced by about 10%, ormore relative to a device not coated with the compound. In someinstances, the formation of biofouling is reduced by about 20%, or morerelative to a device not coated with the compound. In some instances,the formation of biofouling is reduced by about 30%, or more relative toa device not coated with the compound. In some instances, the formationof biofouling is reduced by about 40%, or more relative to a device notcoated with the compound. In some instances, the formation of biofoulingis reduced by about 50%, or more relative to a device not coated withthe compound. In some instances, the formation of biofouling is reducedby about 60%, or more relative to a device not coated with the compound.In some instances, the formation of biofouling is reduced by about 70%,or more relative to a device not coated with the compound. In someinstances, the formation of biofouling is reduced by about 80%, or morerelative to a device not coated with the compound. In some instances,the formation of biofouling is reduced by about 90%, or more relative toa device not coated with the compound. In some instances, the formationof biofouling is reduced by about 95%, or more relative to a device notcoated with the compound. In some instances, the formation of biofoulingis reduced by about 99%, or more relative to a device not coated withthe compound. In some instances, the formation of biofouling is reducedby about 99.5%, or more relative to a device not coated with thecompound. In some instances, the formation of biofouling is reduced byabout 99.9%, or more relative to a device not coated with the compound.In some instances, the compound is a compound that has a structurerepresented by a Formula (I):

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—;    -   L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OR⁹,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O—, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and    -   R^(10b) is —(C═O)—C2-C6alkenyl, —(S═O)—C2-C6alkenyl, or        —(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has the structureselected from:

In some embodiments, the compound of Formula (I) has the followingstructure:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, the compound of Formula (I) has a structureselected from:

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, Z is selected from —CR^(6a)R^(6b)—, —C(═O)—,—C(═NH)—, and —C(═NH)NR⁷—. In some embodiments, Z is —CR^(6a)R^(6b)—. Insome embodiments, Z is —C(═O)—. In some embodiments, Z is —C(═NH)—. Insome embodiments, Z is —C(═NH)NR⁷—.

In some embodiments, each R³ is independently selected from hydrogen,optionally substituted C1-C4 alkyl, —X-optionally substituted C1-C4alkyl, optionally substituted aryl, and —X-optionally substituted aryl.In some embodiments, R³ is hydrogen. In some embodiments, R³ isoptionally substituted C1-C4 alkyl. In some embodiments, R³ is—X-optionally substituted C1-C4 alkyl. In some embodiments, R³ isoptionally substituted aryl. In some embodiments, R³ is —X—optionallysubstituted aryl.

In some embodiments, X is —C(═O)—, —S(═O)—, or —S(═O)₂—. In someembodiments, X is —C(═O)—. In some embodiments, X is —S(═O)—. In someembodiments, X is —S(═O)₂—.

In some embodiments, each R^(6a) and R^(6b) is hydrogen.

In some embodiments, m is 0, 1, 2, 3, 4, or 5. In some embodiments, m is0. In some embodiments, m is 1. In some embodiments, m is 2. In someembodiments, m is 3. In some embodiments, m is 4. In some embodiments, mis 5.

In some embodiments, R^(5a) is hydrogen; R^(5b) is —NR^(10a)R^(10b); andR^(5c) is hydrogen.

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ia):

In some embodiments, the compound of Formula (I) has a structure ofFormula (Ib):

In some embodiments, R^(10a) is hydrogen, optionally substituted C1-C4alkyl, or optionally substituted aryl. In some embodiments, R^(10a) ishydrogen. In some embodiments, R^(10a) is optionally substituted C1-C4alkyl. In some embodiments, R^(10a) is CH₃. In some embodiments, R^(10a)is CH₂CH₃. In some embodiments, R^(10a) is optionally substituted aryl.In some embodiments, R^(10a) is phenyl.

In some embodiments, R^(10b) is —(C═O)—C2-C6alkenyl,—(S═O)—C2-C6alkenyl, or —(S═O)₂—C2-C6alkenyl. In some embodiments,R^(10b) is —(C═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)—C2-C6alkenyl. In some embodiments, R^(10b) is—(S═O)₂—C2-C6alkenyl.

In some embodiments, the compound of Formula (I) has the structure of:

In some embodiments, a compound described above is a compound that has astructure represented by a Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹ and B² is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, B³ is —O—.

In some embodiments, D is —S(═O)₂OR^(9a) or —C(═O)OR^(9a). In someembodiments, D is —S(═O)₂OR^(9a). In some embodiments, D is—C(═O)OR^(9a).

In some embodiments, R^(9a) is hydrogen or —CH₃. In some embodiments,R^(9a) is hydrogen. In some embodiments, R^(9a) is —CH₃.

In some embodiments, D is —S(═O)₂O⁻ or —C(═O)O⁻. In some embodiments, Dis —S(═O)₂O⁻.

In some embodiments, D is —C(═O)O⁻.

In some embodiments, each R^(6c) and R^(Id) is hydrogen.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

In some embodiments, n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is0. In some embodiments, n is 1. In some embodiments, m is 2. In someembodiments, n is 3. In some embodiments, n is 4. In some embodiments, nis 5.

In some embodiments, s is 1, 2, 3, or 4. In some embodiments, s is 1. Insome embodiments, s is 2. In some embodiments, s is 3. In someembodiments, s is 4.

In some embodiments, t is 1, 2, 3, or 4. In some embodiments, t is 1. Insome embodiments, t is 2. In some embodiments, t is 3. In someembodiments, t is 4.

In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. Insome embodiments, p is 2. In some embodiments, p is 3. In someembodiments, p is 4.

In some embodiments, q is 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, or 60. In some embodiments, q is 45,46, 47, 48, 49, 50, 51, 52, 53, 54, or 55. In some embodiments, q is 45.In some embodiments, q is 46. In some embodiments, q is 47. In someembodiments, q is 48. In some embodiments, q is 49. In some embodiments,q is 50. In some embodiments, q is 51. In some embodiments, q is 52. Insome embodiments, q is 53. In some embodiments, q is 54. In someembodiments, q is 55.

In some embodiments, r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In someembodiments, r is 1. In some embodiments, r is 2. In some embodiments, ris 3. In some embodiments, r is 4. In some embodiments, r is 5. In someembodiments, r is 6. In some embodiments, r is 7. In some embodiments, ris 8. In some embodiments, r is 9. In some embodiments, r is 10.

In some embodiments, a compound described above is a compound that has astructure represented by a Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹, B², and B³ is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR⁹a

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+). In some embodiments,each R^(9a), R^(9b), or R^(9c) is independently H or —CH₃. In someembodiments, R^(9a) is H. In some embodiments, R^(9a) is —CH₃. In someembodiments, R^(9b) is H. In some embodiments, R^(9b) is —CH₃. In someembodiments, R^(9c) is H.

In some embodiments, R^(9c) is —CH₃.

In some embodiments, E is —S(═O)₂OR^(9a). In some embodiments, eachR^(9a) is H or —CH₃. In some embodiments, R^(9a) is H. In someembodiments, R^(9a) is —CH₃.

In some embodiments, each R^(6c) and R^(6d) is independently selectedfrom hydrogen and —CH₃.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(12a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

IV. Methods of Making

In a further aspect, described herein is a method of preparing abiofouling-resistant device, comprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a copolymer; and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        copolymer onto the surface of the device, thereby making the        biofouling-resistant device;    -   wherein the copolymer comprises a phenyl azide-based copolymer;        and wherein the copolymer has a number-average molecular weight        of between about 10,000 and about 250,000.

In some embodiments, also described herein is a method of preparing acopolymer modified biofouling-resistant silicon-based device comprising:

-   -   a) contacting a surface of a silicon-based device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        copolymer onto the surface of the silicon-based device, thereby        generating the charged or zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer.

In some embodiments, also described herein is a method of preparing acharged or zwitterion copolymer modified biofouling-resistant devicecomprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   a) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        copolymer onto the surface of the device, thereby generating the        charged or zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer has a number-average molecular weight of between about        10,000 and about 250,000.

In some embodiments, the method comprises one-step grafting reactionthat modifies the surface of a device.

In some embodiments, the device is a medical device described herein. Insome embodiments, the device is a non-medical device described herein.

In some embodiments, the time sufficient to undergo photografting is atleast 1 minute, at least 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20minutes, 25 minutes or 30 minutes.

In some embodiments, the light source is an ultraviolet light source. Insome embodiments, the ultraviolet light source has an intensity of atleast 500 μW/cm². In some embodiments, the ultraviolet light source hasan intensity of at least 600 μW/cm². In some embodiments, theultraviolet light source has an intensity of at least 700 μW/cm². Insome embodiments, the ultraviolet light source has an intensity of atleast 800 μW/cm². In some embodiments, the ultraviolet light source hasan intensity of at least 900 μW/cm². In some embodiments, theultraviolet light source has an intensity of at least 1000 μW/cm².

In some embodiments, the ultraviolet light source has a wavelength ofbetween 240 nm and 280 nm, between 240 nm and 275 nm, between 240 nm and270 nm, between 240 nm and 265 nm, between 240 nm and 260 nm, between240 nm and 255 nm, between 240 nm and 250 nm, between 240 nm and 245 nm,between 250 nm and 280 nm, between 250 nm and 275 nm, between 250 nm and270 nm, between 250 nm and 265 nm, between 250 nm and 260 nm, between255 nm and 280 nm, between 255 nm and 275 nm, between 255 nm and 270 nm,between 255 nm and 265 nm, between 255 nm and 260 nm, between 260 nm and280 nm, between 260 nm and 275 nm, between 260 nm and 270 nm, or between270 nm and 280 nm.

In some embodiments, the ultraviolet light source has a wavelength of atleast 240 nm, 245 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm,256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm,265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 275 nm or 280 nm. Insome embodiments, the ultraviolet light source has a wavelength of nomore than 240 nm, 245 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 275 nm or 280 nm.

In some embodiments, the mixture of step a) is an aqueous solution, anaqueous colloid, or an aqueous suspension. In some embodiments, themixture of step a) is a non-aqueous solution, an aqueous colloid, or anaqueous suspension.

In some embodiments, the phenyl azide-based copolymer is a compound ofFormula (II) or (III) described herein.

In some embodiments, the mixture comprising a charged or zwitterioncopolymer has a concentration of the charged or zwitterion copolymer inthe mixture between 1 mg/mL and 30 mg/mL.

In some embodiments, the concentration of the charged or zwitterioncopolymer in the mixture is between 1 mg/mL and 25 mg/mL, between 1mg/mL and 20 mg/mL, between 1 mg/mL and 15 mg/mL, between 1 mg/mL and 10mg/mL, between 1 mg/mL and 5 mg/mL, between 5 mg/mL and 30 mg/mL,between 5 mg/mL and 25 mg/mL, between 5 mg/mL and 20 mg/mL, between 5mg/mL and 15 mg/mL, between 5 mg/mL and 10 mg/mL, between 10 mg/mL and30 mg/mL, between 10 mg/mL and 25 mg/mL, between 10 mg/mL and 20 mg/mL,between 10 mg/mL and 15 mg/mL, between 15 mg/mL and 30 mg/mL, between 15mg/mL and 25 mg/mL, between 15 mg/mL and 20 mg/mL, between 20 mg/mL and30 mg/mL, or between 20 mg/mL and 25 mg/mL.

In some embodiments, the concentration of the charged or zwitterioncopolymer in the mixture is about 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5mg/mL, 6 mg/mL, 7 mg/mL, 8 mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL,13 mg/mL, 14 mg/mL, 15 mg/mL, 16 mg/mL, 17 mg/mL, 18 mg/mL, 19 mg/mL, 20mg/mL, 21 mg/mL, 22 mg/mL, 23 mg/mL, 24 mg/mL, 25 mg/mL, 26 mg/mL, 27mg/mL, 28 mg/mL, 29 mg/mL, or 30 mg/mL.

In some embodiments, the concentration of the charged or zwitterioncopolymer is between 0.1 to 1 mg per square centimeter of the device.

In some embodiments, the device comprises a polymer-based device. Insome embodiments, the polymer-based device comprises a polyolefinicdevice. In some embodiments, the polyolefinic device comprises a devicemodified with polyethylene (PE), polypropylene (PP), polyamide (PA),polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVdF),polyvinyl chloride (PVC), or a combination thereof. In some embodiments,the device comprises a microporous device or a nonwoven device. In someembodiments, the device comprises a carbon-based device comprising amoiety capable of binding with a compound that has a structure ofFormula (I), (II), or (III). In some embodiments, the carbon-baseddevice comprises a polymer moiety. In some embodiments, the carbon-baseddevice comprises a carbon-based polymer. In some embodiments, thecarbon-based device comprises a polyolefin moiety. In some embodiments,the polyolefin moiety comprises a polyethylene (PE) moiety, apolypropylene (PP) moiety, a polyamide (PA) moiety, apolytetrafluoroethylene (PTFE) moiety, a polyvinylidene fluoride (PVdF)moiety, or a polyvinyl chloride (PVC) moiety. [0365]. In someembodiments, the device comprises a carbon-based device. In someembodiments, the carbon-based device comprises a carbon-based polymer.In some embodiments, the carbon-based device comprises a polyolefinmoiety. In some embodiments, the polyolefin moiety comprisespolyethylene moiety, polypropylene moiety, polyvinyl chloride moiety,polyvinylidene fluoride moiety, polytetrafluoroethylene moiety,polychlorotrifluoroethylene moiety, or polystyrene moiety.

In some embodiments, the carbon-based polymer comprises polyamidemoiety, polyurethane moiety, phenol-formaldehyde resin moiety,polycarbonate moiety, polychloroprene moiety, polyacrylonitrile moiety,polimide moiety, or polyester moiety. In some embodiments, thecarbon-based polymer comprises nylon. In some embodiments, thecarbon-based polymer comprises polyethylene terephthalate.

In some embodiments, the device comprises a silicon-based device. Insome embodiments, the silicon-based device comprises a silicon-basedpolymer moiety. In some embodiments, the device comprises asilicon-based device comprising a moiety capable of binding with acompound that has a structure of Formula (I), (II), or (III). In someembodiments, the silicon-based device comprises a polymer moiety. Insome embodiments, the silicon-based device comprises a siloxane polymermoiety, a sesquisiloxane polymer moiety, a siloxane-silarylene polymermoiety, a silalkylene polymer moiety, a polysilane moiety, apolysilylene moiety, or a polysilazane moiety.

In some embodiments, the silicon-based device comprises a siloxanepolymer moiety. In some embodiments, the silicon-based device comprisessilicone polymer.

In some embodiments, the device comprises a carbon-based device or asilicon-based device.

In some embodiments, the copolymer comprises zwitterionic copolymer. Insome embodiments, the zwitterionic copolymer comprises polysulfobetaine.

In some embodiments, the biofouling of the biofouling-resistant medicaldevice described herein is produced by a bacterium, a virus, and/or afungus.

V. Methods of Synthesis

Methods provided by the present disclosure also include methods ofsynthesizing a compound of Formula (II) comprising: reacting a compoundof Formula (IV) or a salt or solvate thereof with a compound of Formula(V):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) and Formula (V) are each        charged or zwitterionic.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹ and B² is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, B³ is —O—.

In some embodiments, D is —S(═O)₂OR^(9a) or —C(═O)OR^(9a). In someembodiments, D is —S(═O)₂OR^(9a). In some embodiments, D is—C(═O)OR^(9a).

In some embodiments, R^(9a) is hydrogen or —CH₃. In some embodiments,R^(9a) is hydrogen. In some embodiments, R^(9a) is —CH₃.

In some embodiments, D is —S(═O)₂O⁻ or —C(═O)O⁻. In some embodiments, Dis —S(═O)₂O⁻.

In some embodiments, D is —C(═O)O⁻.

In some embodiments, each R^(6c) and R^(6d) is hydrogen.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R^(11c), R^(12b), and R^(12c) ishydrogen.

In some embodiments, n is 0, 1, 2, 3, 4, or 5. In some embodiments, n is0. In some embodiments, n is 1. In some embodiments, m is 2. In someembodiments, n is 3. In some embodiments, n is 4. In some embodiments, nis 5.

In some embodiments, s is 1, 2, 3, or 4. In some embodiments, s is 1. Insome embodiments, s is 2. In some embodiments, s is 3. In someembodiments, s is 4.

In some embodiments, t is 1, 2, 3, or 4. In some embodiments, t is 1. Insome embodiments, t is 2. In some embodiments, t is 3. In someembodiments, t is 4.

In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1. Insome embodiments, p is 2. In some embodiments, p is 3. In someembodiments, p is 4.

In some embodiments, q is 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55.In some embodiments, q is 45. In some embodiments, q is 46. In someembodiments, q is 47. In some embodiments, q is 48. In some embodiments,q is 49. In some embodiments, q is 50. In some embodiments, q is 51. Insome embodiments, q is 52. In some embodiments, q is 53. In someembodiments, q is 54. In some embodiments, q is 55.

In some embodiments, r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In someembodiments, r is 1. In some embodiments, r is 2. In some embodiments, ris 3. In some embodiments, r is 4. In some embodiments, r is 5. In someembodiments, r is 6. In some embodiments, r is 7. In some embodiments, ris 8. In some embodiments, r is 9. In some embodiments, r is 10.

In some embodiments, the compound of Formula (IV) has the structure of:

In some embodiments, the compound of Formula (V) has the structure of:

Methods provided by the present disclosure also include methods ofsynthesizing a compound of Formula (III) comprising: reacting a compoundof Formula (IV) or a salt or solvate thereof with a compound of Formula(VI):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

In some embodiments, each R^(1a) and R^(1b) is independently halogen. Insome embodiments, each R^(1a) and R^(1b) is independently F or Cl. Insome embodiments, each R^(1a) and R^(1b) is F. In some embodiments, eachR^(2a) and R^(2b) is independently selected from halogen, —CN, andoptionally substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is independently halogen. In some embodiments, eachR^(2a) and R^(2b) is —CN. In some embodiments, each R^(2a) and R^(2b) isindependently substituted C1-C6fluoroalkyl. In some embodiments, eachR^(2a) and R^(2b) is —CF₃.

In some embodiments, each R^(1a), R^(1b), R^(2a), and R^(2b) is F.

In some embodiments, A¹ is —S(═O)₂—. In some embodiments, A¹ is —C(═O)—.

In some embodiments, A² is —S(═O)₂—. In some embodiments, A² is —C(═O)—.

In some embodiments, A³ is —S(═O)₂—. In some embodiments, A³ is —C(═O)—.

In some embodiments, each B¹, B², and B³ is —NR^(3c)—.

In some embodiments, each R^(3c) is independently hydrogen, optionallysubstituted C1-C4 alkyl, or optionally substituted aryl. In someembodiments, R^(3c) is hydrogen. In some embodiments, R^(3c) isoptionally substituted C1-C4 alkyl. In some embodiments, R^(3c) is —CH₃.In some embodiments, R^(3c) is optionally substituted aryl. In someembodiments, R^(3c) is optionally substituted phenyl.

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR⁹a

In some embodiments, E is —NR^(9a)R^(9b)R^(9c+). In some embodiments,each R^(9a), R^(9b), or R^(9c) is independently H or —CH₃. In someembodiments, R^(9a) is H. In some embodiments, R^(9a) is —CH₃. In someembodiments, R^(9b) is H. In some embodiments, R^(9b) is —CH₃. In someembodiments, R^(9c) is H.

In some embodiments, R^(9c) is —CH₃.

In some embodiments, E is —S(═O)₂OR^(9a). In some embodiments, eachR^(9a) is H or —CH₃. In some embodiments, R^(9a) is H. In someembodiments, R^(9a) is —CH₃.

In some embodiments, each R^(6c) and R^(6d) is independently selectedfrom hydrogen and —CH₃.

In some embodiments, each R^(3a) and R^(3b) is —CH₃.

In some embodiments, R^(11a) is hydrogen or —CH₃. In some embodiments,R^(11a) is hydrogen. In some embodiments, R^(11a) is —CH₃.

In some embodiments, R^(12a) is hydrogen or —CH₃. In some embodiments,R^(12a) is hydrogen. In some embodiments, R^(12a) is —CH₃.

In some embodiments, each R^(11b), R¹¹, R^(12b), and R^(12c) ishydrogen.

In some embodiments, the compound of Formula (IV) has the structure of:

In some embodiments, the compound of Formula (VI) has the structure of:

In some embodiments, the compound of Formula (VI) has the structure of:

Any combination of the groups described above or below for the variousvariables is contemplated herein. Throughout the specification, groupsand substituents thereof are chosen by one skilled in the field toprovide stable moieties and compounds.

Properties of Biofouling-Resistant Coatings

In some embodiments, biofouling-resistant coatings disclosed herein havevarious properties that provide the superior function of the devices,including excellent flux, improved hydrophilicity, improved resistanceto fouling, tunable surface charge properties, higher thermal stability,higher chemical stability, higher solvent stability, or a combinationthereof. It is also understood that the coatings disclosed herein haveother properties.

In some embodiments, a biofouling-resistant coating disclosed herein hasa water receding angle of less than about 70°. In some embodiments, abiofouling-resistant coating disclosed herein has a water receding angleof less than about 65°. In some embodiments, a biofouling-resistantcoating disclosed herein has a water receding angle of less than about60°. In some embodiments, a biofouling-resistant coating disclosedherein has a water receding angle of less than about 55°. In someembodiments, a biofouling-resistant coating disclosed herein has a waterreceding angle of less than about 50°. In some embodiments, abiofouling-resistant coating disclosed herein has a water receding angleof less than about 45°. In some embodiments, a biofouling-resistantcoating disclosed herein has a water receding angle of less than about40°. In some embodiments, a biofouling-resistant coating disclosedherein has a water receding angle of less than about 35°. In someembodiments, a biofouling-resistant coating disclosed herein has a waterreceding angle of less than about 30°. In some embodiments, abiofouling-resistant coating disclosed herein has a water receding angleof less than about 25°. In some embodiments, a biofouling-resistantcoating disclosed herein has a water receding angle of less than about20°. In some embodiments, a biofouling-resistant coating disclosedherein has a water receding angle of less than about 15°. In someembodiments, a biofouling-resistant coating disclosed herein has a waterreceding angle of less than about 10°. In some embodiments, abiofouling-resistant coating disclosed herein has a water receding angleof less than about 5°. In some embodiments, a biofouling-resistantcoating disclosed herein has a water receding angle of about 0°. Incertain embodiments, the devices provided herein, coated by one or morebiofouling-resistant coatings described herein have a high resistance offouling.

In a further aspect, a biofouling-resistant coating disclosed hereinexhibits an improvement in at least one property selected fromresistance to fouling, hydrophilicity, surface charge, salt rejection,and roughness. In some embodiments, a biofouling-resistant coatingdisclosed herein demonstrates an improvement in at least one propertyselected from resistance to fouling, salt rejection, and hydrophilicity.In some embodiments, a biofouling-resistant coating disclosed hereindemonstrates an improvement in resistance to fouling. In someembodiments, a biofouling-resistant coating disclosed hereindemonstrates an improvement in hydrophilicity. In some embodiments, abiofouling-resistant coating disclosed herein demonstrates animprovement in surface charge. In some embodiments, abiofouling-resistant coating disclosed herein demonstrates animprovement in roughness. In some embodiments, a biofouling-resistantcoating disclosed herein demonstrates reduced surface roughness. In someembodiments, a biofouling-resistant coating disclosed hereindemonstrates an improvement in salt rejection.

In some embodiments, a biofouling-resistant coating disclosed hereincomprising one or more compounds of Formula (I), (II), or (III)described herein prevents and/or reduces biofouling. In some instances,biofouling comprises microfouling or macrofouling. Microfoulingcomprises formation of microorganism adhesion (e.g., bacteria adhesion)and/or biofilm. Biofilm is a group of microorganism which adheres to asurface. In some instances, the adhered microorganisms are furtherembedded in a self-produced matrix of extracellular polymeric substance,which comprises a polymeric conglomeration of extracellular DNA,protein, and polysaccharides. Macrofouling comprises attachment oflarger organism. In some instances a biofouling-resistant coatingdisclosed herein prevents and/or reduces microfouling. In someinstances, a biofouling-resistant coating disclosed herein preventsand/or reduces bacterial adhesion. In some instances, abiofouling-resistant coating disclosed herein prevents and/or reducesbiofilm. In other instances, a biofouling-resistant coating disclosedherein prevents and/or reduces macrofouling.

Microfouling

In some instances, microfouling is formed by bacteria or fungi. In someinstances, microfouling is formed by bacteria. In some instances, abacterium is a gram-positive bacterium or a gram-negative bacterium. Insome cases, a bacterium is a marine bacterium.

In some cases, microfouling is formed by a gram-positive bacterium.Exemplary gram-positive bacteria include, but are not limited to,bacteria from the genus Actinomyces, Arthrobacter, Bacillus,Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria,Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. In someinstances, a gram-positive bacterium comprises Actinomyces spp.,Arthrobacter spp., Bacillus lichenformis, Clostridium difficile,Clostridium spp., Corynebacterium spp., Enterococcus faecalis,Lactococcus spp., Listeria monocytogenes, Micrococcus spp.,Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis,Streptococcus pneumoniae, or Streptococcus pyogenes.

In some instances, microfouling is formed by a gram-positive bacteriumfrom the genus Actinomyces, Arthrobacter, Bacillus, Clostridium,Corynebacterium, Enterococcus, Lactococcus, Listeria, Micrococcus,Mycobacterium, Staphylococcus, or Streptococcus. In some instances,microfouling is formed by a gram-positive bacterium: Actinomyces spp.,Arthrobacter spp., Bacillus licheniformis, Clostridium difficile,Clostridium spp., Corynebacterium spp., Enterococcus faecalis,Lactococcus spp., Listeria monocytogenes, Micrococcus spp.,Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis,Streptococcus pneumoniae, or Streptococcus pyogenes.

In some instances, a biofouling-resistant coating disclosed herein isresistant to fouling. In some instances, a biofouling-resistant coatingdisclosed herein prevents and/or reduces microfouling on one or more ofits surfaces. In some cases, a biofouling-resistant coating disclosedherein prevents and/or reduces microfouling formed by a gram-positivebacterium from the genus Actinomyces, Arthrobacter, Bacillus,Clostridium, Corynebacterium, Enterococcus, Lactococcus, Listeria,Micrococcus, Mycobacterium, Staphylococcus, or Streptococcus. In somecases, a biofouling-resistant coating disclosed herein prevents and/orreduces microfouling formed by a gram-positive bacterium: Actinomycesspp., Arthrobacter spp., Bacillus licheniformis, Clostridium difficile,Clostridium spp., Corynebacterium spp., Enterococcus faecalis,Lactococcus spp., Listeria monocytogenes, Micrococcus spp.,Mycobacterium spp., Staphylococcus aureus, Staphylococcus epidermidis,Streptococcus pneumoniae, or Streptococcus pyogenes.

In some cases, microfouling comprises bacteria adhesion. In someinstances, a biofouling-resistant coating disclosed herein preventsand/or reduces bacteria adhesion. In some cases, a biofouling-resistantcoating disclosed herein prevents and/or reduces bacteria adhesionformed by a gram-positive bacterium from the genus Actinomyces,Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus,Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, orStreptococcus. In some cases, a biofouling-resistant coating disclosedherein coated onto a material prevents and/or reduces bacteria adhesionformed by a gram-positive bacterium: Actinomyces spp., Arthrobacterspp., Bacillus licheniformis, Clostridium difficile, Clostridium spp.,Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeriamonocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcusaureus, Staphylococcus epidermidis, Streptococcus pneumoniae, orStreptococcus pyogenes.

In some cases, microfouling comprises biofilm. In some instances, abiofouling-resistant coating disclosed herein coated onto a materialprevents and/or reduces biofilm. In some cases, a biofouling-resistantcoating disclosed herein coated onto a material prevents and/or reducesbiofilm formed by a gram-positive bacterium from the genus Actinomyces,Arthrobacter, Bacillus, Clostridium, Corynebacterium, Enterococcus,Lactococcus, Listeria, Micrococcus, Mycobacterium, Staphylococcus, orStreptococcus. In some cases, a biofouling-resistant coating disclosedherein coated onto a material prevents and/or reduces biofilm formed bya gram-positive bacterium: Actinomyces spp., Arthrobacter spp., Bacilluslicheniformis, Clostridium difficile, Clostridium spp., Corynebacteriumspp., Enterococcus faecalis, Lactococcus spp., Listeria monocytogenes,Micrococcus spp., Mycobacterium spp., Staphylococcus aureus,Staphylococcus epidermidis, Streptococcus pneumoniae, or Streptococcuspyogenes.

In some cases, microfouling is formed by a gram-negative bacterium.Exemplary gram-negative bacteria include, but are not limited to,bacteria from the genus Alteromonas, Aeromonas, Desulfovibrio,Escherichia, Fusobacterium, Geobacter, Haemophilus, Klebsiella,Legionella, Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella,Salmonella, or Vibrio. In some instances, a gram-negative bacteriumcomprises Alteromonas spp., Aeromonas spp., Desulfovibrio spp.,Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilusspp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp.,Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteuspenneri, Serratia spp., Shigella dysenteriae, Shigella flexneri,Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonellaenterica, or Vibrio Cholerae.

In some instances, microfouling is formed by a gram-negative bacteriumfrom the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia,Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella,Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, orVibrio. In some instances, microfouling is formed by a gram-negativebacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp.,Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilusspp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp.,Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteuspenneri, Serratia spp., Shigella dysenteriae, Shigella flexneri,Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonellaenterica, or Vibrio Cholerae.

In some embodiments, a biofouling-resistant coating disclosed hereinprevents and/or reduces microfouling formed by a gram-negative bacteriumfrom the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia,Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella,Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, orVibrio. In some instances, a biofouling-resistant coating disclosedherein prevents and/or reduces microfouling formed by a gram-negativebacterium: Alteromonas spp., Aeromonas spp., Desulfovibrio spp.,Escherichia coli, Fusobacterium nucleatum, Geobacter spp., Haemophilusspp., Klebsiella spp., Legionella pneumophila, Porphyromonas spp.,Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Proteuspenneri, Serratia spp., Shigella dysenteriae, Shigella flexneri,Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonellaenterica, or Vibrio Cholerae.

In some embodiments, microfouling comprises bacteria adhesion. In someembodiments, a biofouling-resistant coating disclosed herein preventsand/or reduces bacteria adhesion formed by a gram-negative bacteriumfrom the genus Alteromonas, Aeromonas, Desulfovibrio, Escherichia,Fusobacterium, Geobacter, Haemophilus, Klebsiella, Legionella,Porphyromonas, Proteus, Pseudomonas, Serratia, Shigella, Salmonella, orVibrio. In some instances, a biofouling-resistant coating disclosedherein prevents and/or reduces bacteria adhesion formed by agram-negative bacterium: Alteromonas spp., Aeromonas spp., Desulfovibriospp., Escherichia coli, Fusobacterium nucleatum, Geobacter spp.,Haemophilus spp., Klebsiella spp., Legionella pneumophila, Porphyromonasspp., Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis,Proteus penneri, Serratia spp., Shigella dysenteriae, Shigella flexneri,Shigella boydii, Shigella sonnei, Salmonella bongori, Salmonellaenterica, or Vibrio Cholerae.

In some instances, microfouling comprises biofilm. In some embodiments,a biofouling-resistant coating disclosed herein prevents and/or reducesbiofilm formed by a gram-negative bacterium from the genus Alteromonas,Aeromonas, Desulfovibrio, Escherichia, Fusobacterium, Geobacter,Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus,Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio. In someinstances, a biofouling-resistant coating disclosed herein preventsand/or reduces biofilm formed by a gram-negative bacterium: Alteromonasspp., Aeromonas spp., Desulfovibrio spp., Escherichia coli,Fusobacterium nucleatum, Geobacter spp., Haemophilus spp., Klebsiellaspp., Legionella pneumophila, Porphyromonas spp., Pseudomonasaeruginosa, Proteus vulgaris, Proteus mirabilis, Proteus penneri,Serratia spp., Shigella dysenteriae, Shigella flexneri, Shigella boydii,Shigella sonnei, Salmonella bongori, Salmonella enterica, or VibrioCholerae.

In some cases, microfouling is formed by a marine bacterium. In someinstances, a marine bacterium comprises Pseudoalteromonas spp. orShewanella spp. In some cases, microfouling is formed byPseudoalteromonas spp. or Shewanella spp.

In some embodiments, a biofouling-resistant coating disclosed hereinprevents and/or reduces microfouling formed by a marine bacterium. Insome cases, a biofouling-resistant coating disclosed herein preventsand/or reduces microfouling formed by Pseudoalteromonas spp. orShewanella spp.

In some instances, microfouling comprises bacteria adhesion. In someembodiments, a biofouling-resistant coating disclosed herein preventsand/or reduces bacteria adhesion formed by a marine bacterium. In somecases, a biofouling-resistant coating disclosed herein prevents and/orreduces bacteria adhesion formed by Pseudoalteromonas spp. or Shewanellaspp.

In some instances, microfouling comprises biofilm. In some embodiments,a biofouling-resistant coating disclosed herein prevents and/or reducesbiofilm formed by a marine bacterium. In some cases, abiofouling-resistant coating disclosed herein prevents and/or reducesbiofilm formed by Pseudoalteromonas spp. or Shewanella spp.

In some embodiments, microfouling is formed by a fungus. Exemplaryfungus includes, but is not limited to, Candida albicans, Candidaglabrata, Candida rugose, Candida parapsilosis, Candida tropicalis,Candida dubliniensis, or Hormoconis resinae. In some cases, microfoulingis formed by Candida albicans, Candida glabrata, Candida rugose, Candidaparapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconisresinae.

In some embodiments, a biofouling-resistant coating disclosed hereinprevents and/or reduces microfouling formed by a fungus. In some cases,a biofouling-resistant coating disclosed herein prevents and/or reducesmicrofouling formed by Candida albicans, Candida glabrata, Candidarugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis,or Hormoconis resinae.

In some instances, microfouling comprises bacteria adhesion. In someembodiments, a biofouling-resistant coating disclosed herein preventsand/or reduces bacteria adhesion formed by a fungus. In some cases, abiofouling-resistant coating disclosed herein prevents and/or reducesbacteria adhesion formed by Candida albicans, Candida glabrata, Candidarugose, Candida parapsilosis, Candida tropicalis, Candida dubliniensis,or Hormoconis resinae.

In some instances, microfouling comprises biofilm. In some embodiments,a biofouling-resistant coating disclosed herein prevents and/or reducesbiofilm formed by a fungus. In some cases, a biofouling-resistantcoating disclosed herein prevents and/or reduces biofilm formed byCandida albicans, Candida glabrata, Candida rugose, Candidaparapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconisresinae.

Macrofouling

In some embodiments, macrofouling comprises calcareous fouling organismor non-calcareous fouling organism. A calcareous fouling organism is anorganism with a hard body. In some cases, calcareous fouling organismscomprise barnacle, bryozoan, mollusk, polychaete, tube worm, or zebramussel. A non-calcareous fouling organism comprises a soft body.Non-calcareous fouling organism comprises seaweed, hydroids, or algae.

In some instances, macrofouling is formed by a calcareous foulingorganism. In some cases, macrofouling is formed by barnacle, bryozoan,mollusk, polychaete, tube worm, or zebra mussel.

In some embodiments, a biofouling-resistant coating disclosed hereinprevents and/or reduces macrofouling formed by a calcareous foulingorganism. In some instances, a biofouling-resistant coating disclosedherein prevents and/or reduces macrofouling formed by barnacle,bryozoan, mollusk, polychaete, tube worm, or zebra mussel.

In some cases, macrofouling is formed by a non-calcareous foulingorganism. In some cases, macrofouling is formed by seaweed, hydroids, oralgae.

In some embodiments, also disclosed herein are biofouling-resistantcoating preventing and/or reducing macrofouling formed by anon-calcareous fouling organism. In some instances, abiofouling-resistant coating disclosed herein prevents and/or reducesmacrofouling formed by seaweed, hydroids, or algae.

In some embodiments, a biofouling-resistant coating disclosed hereinreduces the formation of biofouling on its surface. In some cases, theformation of biofouling on a surface of a device modified with acompound of Formula (I), (II), or (III) is reduced by about 10%, 20%,30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or morerelative to the unmodified surface of a device. In some instances, theformation of biofouling is reduced by at least about 10%, 20%, 30%, 40%,50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or more relative to theunmodified surface of a device. In some instances, the formation ofbiofouling relative to the unmodified surface of a device is determinedby comparing the amount of biofouling following a period of time ofstorage, use, and/or testing of the device(s). For example, the devicesmay be tested by exposing them to conditions conducive of biofoulingformation (e.g., in vitro biofouling testing techniques known andpracticed in the art). In some instances, the formation of biofouling isreduced by about 10%, or more relative to the unmodified surface of adevice. In some instances, the formation of biofouling is reduced byabout 20%, or more relative to the unmodified surface of a device. Insome instances, the formation of biofouling is reduced by about 30%, ormore relative to the unmodified surface of a device. In some instances,the formation of biofouling is reduced by about 40%, or more relative tothe unmodified surface of a device. In some instances, the formation ofbiofouling is reduced by about 50%, or more relative to the unmodifiedsurface of a device. In some instances, the formation of biofouling isreduced by about 60%, or more relative to the unmodified surface of adevice. In some instances, the formation of biofouling is reduced byabout 70%, or more relative to the unmodified surface of a device. Insome instances, the formation of biofouling is reduced by about 80%, ormore relative to the unmodified surface of a device. In some instances,the formation of biofouling is reduced by about 90%, or more relative tothe unmodified surface of a device. In some instances, the formation ofbiofouling is reduced by about 95%, or more relative to the unmodifiedsurface of a device. In some instances, the formation of biofouling isreduced by about 99%, or more relative to the unmodified surface of adevice. In some instances, the formation of biofouling is reduced byabout 99.5%, or more relative to the unmodified surface of a device. Insome instances, the formation of biofouling is reduced by about 99.9%,or more relative to the unmodified surface of a device.

In some embodiments, a biofouling-resistant coating disclosed herein isfurther coated with an additional agent. In some instances, theadditional agent is an antimicrobial agent. Exemplary antimicrobialagent comprises quaternary ammonium salts or tertiary amines. In someinstances, the additional agent is a chemical disinfectant. Exemplarychemical disinfectant comprises sodium hypochlorite, sodium hydroxide,and benzalkonium chloride.

Definitions

As used herein, nomenclature for compounds, including organic compounds,can be given using common names, IUPAC, IUBMB, or CAS recommendationsfor nomenclature. When one or more stereochemical features are present,Cahn-Ingold-Prelog rules for stereochemistry can be employed todesignate stereochemical priority, E Z specification, and the like. Oneof skill in the art can readily ascertain the structure of a compound ifgiven a name, either by systemic reduction of the compound structureusing naming conventions, or by commercially available software, such asCHEMDRAW™ (Cambridgesoft Corporation, U.S.A.).

As used in the specification and the appended claims, the singular forms“a,” “an” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a component,” “apolymer,” or “a particle” includes mixtures of two or more suchcomponents, polymers, or particles, and the like.

Ranges can be expressed herein as from “about” one particular value,and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value and/orto the other particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. It will be furtherunderstood that the endpoints of each of the ranges are significant bothin relation to the other endpoint, and independently of the otherendpoint. It is also understood that there are a number of valuesdisclosed herein, and that each value is also herein disclosed as“about” that particular value in addition to the value itself. Forexample, if the value “10” is disclosed, then “about 10” is alsodisclosed. It is also understood that when a value is disclosed that“less than or equal to” the value, “greater than or equal to the value”and possible ranges between values are also disclosed, as appropriatelyunderstood by the skilled artisan. For example, if the value “10” isdisclosed the “less than or equal to 10” as well as “greater than orequal to 10” is also disclosed. It is also understood that throughoutthe application, data is provided in a number of different formats andthat this data represents endpoints and starting points, and ranges forany combination of the data points. For example, if a particular datapoint “10” and a particular data point 15 are disclosed, it isunderstood that greater than, greater than or equal to, less than, lessthan or equal to, and equal to 10 and 15 are considered disclosed aswell as between 10 and 15. It is also understood that each unit betweentwo particular units are also disclosed. For example, if 10 and 15 aredisclosed, then 11, 12, 13, and 14 are also disclosed.

References in the specification and concluding claims to parts by weightof a particular element or component in a composition denotes the weightrelationship between the element or component and any other elements orcomponents in the composition or article for which a part by weight isexpressed. Thus, in a compound containing 2 parts by weight of componentX and 5 parts by weight component Y, X and Y are present at a weightratio of 2:5, and are present in such ratio regardless of whetheradditional components are contained in the compound.

A weight percent (wt. %) of a component, unless specifically stated tothe contrary, is based on the total weight of the formulation orcomposition in which the component is included.

As used herein, the terms “optional” or “optionally” means that thesubsequently described event or circumstance may or may not occur, andthat the description includes instances where said event or circumstanceoccurs and instances where it does not.

As used herein, the terms “effective amount” and “amount effective”refer to an amount that is sufficient to achieve the desired result orto have an effect on an undesired condition.

The term “stable”, as used herein, refers to compositions that are notsubstantially altered when subjected to conditions to allow for theirproduction, detection, and, in certain aspects, their recovery,purification, and use for one or more of the purposes disclosed herein.

As used herein, the term “polymer” refers to a relatively high molecularweight organic compound, natural or synthetic, whose structure can berepresented by a repeated small unit, the monomer (e.g., polyethylene,rubber, cellulose). Synthetic polymers are typically formed by additionor condensation polymerization of monomers. Unless indicated otherwise,polymer molecular weights are given in Daltons.

As used herein, the term “homopolymer” refers to a polymer formed from asingle type of repeating unit (monomer residue).

As used herein, the term “copolymer” refers to a polymer formed from twoor more different repeating units (monomer residues). By way of exampleand without limitation, a copolymer can be an alternating copolymer, arandom copolymer, a block copolymer, or a graft copolymer. It is alsocontemplated that, in certain aspects, various block segments of a blockcopolymer can themselves comprise copolymers.

As used herein, the term “oligomer” refers to a relatively low molecularweight polymer in which the number of repeating units is between two andten, for example, from two to eight, from two to six, or form two tofour. In one aspect, a collection of oligomers can have an averagenumber of repeating units of from about two to about ten, for example,from about two to about eight, from about two to about six, or formabout two to about four.

As used herein, the term “cross-linked polymer” refers to a polymerhaving bonds linking one polymer chain to another.

As used herein, the term “porogen composition” or “porogen(s)” refers toany structured material that can be used to create a porous material.

“Oxo” refers to the ═O substituent.

“Thioxo” refers to the ═S substituent.

“Alkyl” refers to a straight or branched hydrocarbon chain radical,having from one to twenty carbon atoms, and which is attached to therest of the molecule by a single bond. An alkyl comprising up to 10carbon atoms is referred to as a C1-C10 alkyl, likewise, for example, analkyl comprising up to 6 carbon atoms is a C1-C6 alkyl. Alkyls (andother moieties defined herein) comprising other numbers of carbon atomsare represented similarly. Alkyl groups include, but are not limited to,C1-C10 alkyl, C1-C9 alkyl, C1-C8 alkyl, C1-C7 alkyl, C1-C6 alkyl, C1-C5alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, C2-C8 alkyl, C3-C8 alkyland C4-C8 alkyl. Representative alkyl groups include, but are notlimited to, methyl, ethyl, n-propyl, 1-methylethyl (i-propyl), n-butyl,i-butyl, s-butyl, n-pentyl, 1,1-dimethylethyl (t-butyl), 3-methylhexyl,2-methylhexyl, 1-ethyl-propyl, and the like. In some embodiments, thealkyl is methyl or ethyl. In some embodiments, the alkyl is —CH(CH3)2 or—C(CH3)3. Unless stated otherwise specifically in the specification, analkyl group may be optionally substituted as described below. “Alkylene”or “alkylene chain” refers to a straight or branched divalenthydrocarbon chain linking the rest of the molecule to a radical group.In some embodiments, the alkylene is —CH2-, —CH2CH2-, or —CH2CH2CH2-. Insome embodiments, the alkylene is —CH2-. In some embodiments, thealkylene is —CH2CH2-. In some embodiments, the alkylene is —CH2CH2CH2-.

“Alkoxy” refers to a radical of the formula —OR where R is an alkylradical as defined. Unless stated otherwise specifically in thespecification, an alkoxy group may be optionally substituted asdescribed below. Representative alkoxy groups include, but are notlimited to, methoxy, ethoxy, propoxy, butoxy, pentoxy. In someembodiments, the alkoxy is methoxy. In some embodiments, the alkoxy isethoxy.

“Heteroalkylene” refers to an alkyl radical as described above where oneor more carbon atoms of the alkyl is replaced with a O, N or S atom.“Heteroalkylene” or “heteroalkylene chain” refers to a straight orbranched divalent heteroalkyl chain linking the rest of the molecule toa radical group. Unless stated otherwise specifically in thespecification, the heteroalkyl or heteroalkylene group may be optionallysubstituted as described below. Representative heteroalkyl groupsinclude, but are not limited to —OCH2OMe, —OCH2CH2OMe, or—OCH2CH2OCH2CH2NH2.

Representative heteroalkylene groups include, but are not limited to—OCH2CH2O—, —OCH2CH2OCH2CH2O—, or —OCH2CH2OCH2CH2OCH2CH2O—.

“Alkylamino” refers to a radical of the formula —NHR or —NRR where eachR is, independently, an alkyl radical as defined above. Unless statedotherwise specifically in the specification, an alkylamino group may beoptionally substituted as described below.

The term “aromatic” refers to a planar ring having a delocalizedπ-electron system containing 4n+2π electrons, where n is an integer.Aromatics can be optionally substituted. The term “aromatic” includesboth aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups(e.g., pyridinyl, quinolinyl).

“Aryl” refers to an aromatic ring wherein each of the atoms forming thering is a carbon atom. Aryl groups can be optionally substituted.Examples of aryl groups include, but are not limited to phenyl, andnaphthyl. In some embodiments, the aryl is phenyl. Depending on thestructure, an aryl group can be a monoradical or a diradical (i.e., anarylene group). Unless stated otherwise specifically in thespecification, the term “aryl” or the prefix “ar-” (such as in“aralkyl”) is meant to include aryl radicals that are optionallysubstituted.

“Carboxy” refers to —CO2H. In some embodiments, carboxy moieties may bereplaced with a “carboxylic acid bioisostere”, which refers to afunctional group or moiety that exhibits similar physical and/orchemical properties as a carboxylic acid moiety. A carboxylic acidbioisostere has similar biological properties to that of a carboxylicacid group. A compound with a carboxylic acid moiety can have thecarboxylic acid moiety exchanged with a carboxylic acid bioisostere andhave similar physical and/or biological properties when compared to thecarboxylic acid-containing compound. For example, in one embodiment, acarboxylic acid bioisostere would ionize at physiological pH to roughlythe same extent as a carboxylic acid group. Examples of bioisosteres ofa carboxylic acid include, but are not limited to:

and the like.

“Cycloalkyl” refers to a monocyclic or polycyclic non-aromatic radical,wherein each of the atoms forming the ring (i.e. skeletal atoms) is acarbon atom. Cycloalkyls may be saturated, or partially unsaturated.Cycloalkyls may be fused with an aromatic ring (in which case thecycloalkyl is bonded through a non-aromatic ring carbon atom).Cycloalkyl groups include groups having from 3 to 10 ring atoms.Representative cycloalkyls include, but are not limited to, cycloalkylshaving from three to ten carbon atoms, from three to eight carbon atoms,from three to six carbon atoms, or from three to five carbon atoms.Monocyclic cyclcoalkyl radicals include, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Insome embodiments, the monocyclic cyclcoalkyl is cyclopropyl, cyclobutyl,cyclopentyl or cyclohexyl. In some embodiments, the monocycliccyclcoalkyl is cyclopentyl. Polycyclic radicals include, for example,adamantyl, norbornyl, decalinyl, and 3,4-dihydronaphthalen-1(2H)-one.Unless otherwise stated specifically in the specification, a cycloalkylgroup may be optionally substituted.

“Fused” refers to any ring structure described herein which is fused toan existing ring structure. When the fused ring is a heterocyclyl ringor a heteroaryl ring, any carbon atom on the existing ring structurewhich becomes part of the fused heterocyclyl ring or the fusedheteroaryl ring may be replaced with a nitrogen atom.

“Halo” or “halogen” refers to bromo, chloro, fluoro or iodo.

“Haloalkyl” refers to an alkyl radical, as defined above, that issubstituted by one or more halo radicals, as defined above, e.g.,trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl,2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl,1,2-dibromoethyl, and the like. Unless stated otherwise specifically inthe specification, a haloalkyl group may be optionally substituted.

“Haloalkoxy” refers to an alkoxy radical, as defined above, that issubstituted by one or more halo radicals, as defined above, e.g.,trifluoromethoxy, difluoromethoxy, fluoromethoxy, trichloromethoxy,2,2,2-trifluoroethoxy, 1,2-difluoroethoxy, 3-bromo-2-fluoropropoxy,1,2-dibromoethoxy, and the like. Unless stated otherwise specifically inthe specification, a haloalkoxy group may be optionally substituted.

“Heterocycloalkyl” or “heterocyclyl” or “heterocyclic ring” refers to astable 3- to 14-membered non-aromatic ring radical comprising 2 to 10carbon atoms and from one to 4 heteroatoms selected from the groupconsisting of nitrogen, oxygen, and sulfur. Unless stated otherwisespecifically in the specification, the heterocycloalkyl radical may be amonocyclic, or bicyclic ring system, which may include fused (when fusedwith an aryl or a heteroaryl ring, the heterocycloalkyl is bondedthrough a non-aromatic ring atom) or bridged ring systems. The nitrogen,carbon or sulfur atoms in the heterocyclyl radical may be optionallyoxidized. The nitrogen atom may be optionally quaternized. Theheterocycloalkyl radical is partially or fully saturated. Examples ofsuch heterocycloalkyl radicals include, but are not limited to,dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl,imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl,octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl,piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl,thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl,thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl,1,1-dioxo-thiomorpholinyl. The term heterocycloalkyl also includes allring forms of carbohydrates, including but not limited tomonosaccharides, disaccharides and oligosaccharides. Unless otherwisenoted, heterocycloalkyls have from 2 to 10 carbons in the ring. In someembodiments, heterocycloalkyls have from 2 to 8 carbons in the ring. Insome embodiments, heterocycloalkyls have from 2 to 8 carbons in the ringand 1 or 2 N atoms. In some embodiments, heterocycloalkyls have from 2to 10 carbons, 0-2 N atoms, 0-2 O atoms, and 0-1 S atoms in the ring. Insome embodiments, heterocycloalkyls have from 2 to 10 carbons, 1-2 Natoms, 0-1 O atoms, and 0-1 S atoms in the ring. It is understood thatwhen referring to the number of carbon atoms in a heterocycloalkyl, thenumber of carbon atoms in the heterocycloalkyl is not the same as thetotal number of atoms (including the heteroatoms) that make up theheterocycloalkyl (i.e. skeletal atoms of the heterocycloalkyl ring).Unless stated otherwise specifically in the specification, aheterocycloalkyl group may be optionally substituted.

“Heteroaryl” refers to an aryl group that includes one or more ringheteroatoms selected from nitrogen, oxygen and sulfur. The heteroaryl ismonocyclic or bicyclic. Illustrative examples of monocyclic heteroarylsinclude pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl,pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl,isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl,thiadiazolyl, furazanyl, indolizine, indole, benzofuran, benzothiophene,indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline,cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, andpteridine. Illustrative examples of monocyclic heteroaryls includepyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl,tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl,isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl,thiadiazolyl, and furazanyl. Illustrative examples of bicyclicheteroaryls include indolizine, indole, benzofuran, benzothiophene,indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline,cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, andpteridine. In some embodiments, heteroaryl is pyridinyl, pyrazinyl,pyrimidinyl, thiazolyl, thienyl, thiadiazolyl or furyl. In someembodiments, a heteroaryl contains 0-4 N atoms in the ring. In someembodiments, a heteroaryl contains 1-4 N atoms in the ring. In someembodiments, a heteroaryl contains 0-4 N atoms, 0-1 O atoms, and 0-1 Satoms in the ring. In some embodiments, a heteroaryl contains 1-4 Natoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments,heteroaryl is a C1-C9heteroaryl. In some embodiments, monocyclicheteroaryl is a C1-C5heteroaryl. In some embodiments, monocyclicheteroaryl is a 5-membered or 6-membered heteroaryl. In someembodiments, a bicyclic heteroaryl is a C6-C9heteroaryl.

The term “optionally substituted” or “substituted” means that thereferenced group may be substituted with one or more additional group(s)individually and independently selected from alkyl, haloalkyl,cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —OH, alkoxy, aryloxy,alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone,arylsulfone, —CN, alkyne, C1-C6alkylalkyne, halogen, acyl, acyloxy,—CO₂H, —CO₂alkyl, nitro, and amino, including mono- and di-substitutedamino groups (e.g. —NH₂, —NHR, —N(R)₂), and the protected derivativesthereof. In some embodiments, optional substituents are independentlyselected from alkyl, alkoxy, haloalkyl, cycloalkyl, halogen, —CN, —NH₂,—NH(CH₃), —N(CH₃)₂, —OH, —CO₂H, and —CO₂alkyl. In some embodiments,optional substituents are independently selected from fluoro, chloro,bromo, iodo, —CH₃, —CH₂CH₃, —CF₃, —OCH₃, and —OCF₃. In some embodiments,substituted groups are substituted with one or two of the precedinggroups. In some embodiments, an optional substituent on an aliphaticcarbon atom (acyclic or cyclic, saturated or unsaturated carbon atoms,excluding aromatic carbon atoms) includes oxo (═O). Compounds describedherein can contain one or more double bonds and, thus, potentially giverise to cis/trans (E/Z) isomers, as well as other conformationalisomers. Unless stated to the contrary, the compounds disclosed hereininclude all such possible isomers, as well as mixtures of such isomers.

In some embodiments, PSB and PFPA-PSB are used interchangeably and referto poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate).

Certain materials, compounds, compositions, and components disclosedherein can be obtained commercially or readily synthesized usingtechniques generally known to those of skill in the art. For example,the starting materials and reagents used in preparing the disclosedcompounds and compositions are either available from commercialsuppliers such as Aldrich Chemical Co., Milwaukee, Wis.), Acros Organics(Morris Plains, N.J.), Fisher Scientific (Pittsburgh, Pa.), or Sigma(St. Louis, Mo.) or are prepared by methods known to those skilled inthe art following procedures set forth in references such as Fieser andFieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley andSons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 andSupplemental volumes (Elsevier Science Publishers, 1989); OrganicReactions, Volumes 1-40 (John Wiley and Sons, 1991); March's AdvancedOrganic Chemistry, (John Wiley and Sons, 4th Edition); and Larock'sComprehensive Organic Transformations (VCH Publishers Inc., 1989).

Unless otherwise expressly stated, it is in no way intended that anymethod set forth herein be construed as requiring that its steps beperformed in a specific order. Accordingly, where a method claim doesnot actually recite an order to be followed by its steps or it is nototherwise specifically stated in the claims or descriptions that thesteps are to be limited to a specific order, it is no way intended thatan order be inferred, in any respect. This holds for any possiblenon-express basis for interpretation, including: matters of logic withrespect to arrangement of steps or operational flow; plain meaningderived from grammatical organization or punctuation; and the number ortype of embodiments described in the specification.

EXAMPLES

The following examples are provided for illustrative purposes only, andare intended to be purely exemplary of the disclosure and are notintended to limit the scope of the claims provided herein. Efforts havebeen made to ensure accuracy with respect to numbers (e.g., amounts,temperature, etc.), but some errors and deviations should be accountedfor.

Materials

α-Bromoisobutyryl bromide, N-Boc-ethanolamine, Trifluoroacetic acid,1,1,4,7,10,10-Hexamethyltriethylenetetramine (97%), [2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, tetrabutylammoniumchloride, and cupper(I) chloride were used as received from SigmaAldrich. Sodium bicarbonate, methylene chloride, magnesium sulfate, and2,2,2-trifluoroethanol were purchased from Alfa Aesar. Sylgard 184 kit(Dow Corning) was obtained from Fisher Chemical.

The zwitterionic polymer, polysulfobetaine (PSB), was selected as anantifouling component of the coating. By adsorbing waterelectrostatically, PSB coatings form a thin hydration barrier thatprevents organic material from adhering to its surface. Commonly usedapproaches to attach PSB coatings to surfaces such as radical-initiatedgraft polymerizations of PSB-methacrylate necessitate the use ofoxygen-free conditions, preconditioning steps, or long reaction timesthat do not meet the scalability requirements. To circumvent the use ofair-free graft polymerizations, we employed perfluorophenylazide (PFPA)as a molecular anchor to graft the PSB coating to the surface ofpolymeric materials under ambient conditions. When triggered withUV-light, PFPA moieties generate a highly reactive nitrene that formscovalent bonds with materials containing amines, C═C double bonds, andC—H bonds. With this method, it was surprisingly found that PSB israpidly coated to a variety of substrates using UV light under ambientconditions with no preconditioning steps needed. In addition, it wasunexpectedly found that water provided an optimal solvent forphotografting of PFPA-PSB coating and that photografting of PFPA-PSB didnot proceed well in the presence of organic solvents.

Example 1. Synthesis of ATRP Initiator 2-Aminoethyl 2-Bromoisobutyrate

ATRP initiator 2-aminoethyl 2-bromoisobutyrate was synthesized accordingto the following procedure. 5 g of 2-bromoisobutyryl bromide was addedto a solution of 3.8 g of t-Boc-aminoethyl alcohol and 2.5 g oftriethylamine in 12 ml methylene chloride in an ice bath. After 16 h,the salts were filtered off and the filtrate was extracted withsaturated sodium bicarbonate solution. Methylene chloride phase wasdried over magnesium sulfate and evaporated. The resultingt-Boc-aminoethyl 2-bromoisobutyrate was treated by 15 ml trifluoroaceticacid (TFA) for 2 h and crystallized upon addition of ethyl ether (yield85%).

Example 2. Synthesis of Perfluorophenylazide Methacrylamide

1.00 g N-(3-amino-propyl)-methacrylamide and 1.41 g triethylamine wasdissolved in 40 mL chloroform at 25° C. and stirred for 1 hour. Thesolution was then cooled to 0° C. Separately a solution of 1.45 gpentafluorobenzene sulfonyl chloride and 0.85 g triethylamine in 10 mLchloroform was also brought to 0° C., then slowly added to the reactiondropwise. The reaction mixture was placed in an ice bath and allowed tocome to room temperature. After 24 hours, the reaction was washed 3Xwith DI water and the organic layer was evaporated under reducedpressure. The resulting product was then dissolved in 40 mL of 3:1acetone:water. 1.5 g sodium azide was then added. After 24 hours, thereaction was partitioned with chloroform and water. The organic layerwas washed 3X with DI water and evaporated under reduced pressureaffording approximately 1.2 g of the perfluorophenylazide methacylamideproduct.

Example 3. Polymerization of Poly(SulfobetaineMethacrylate-Co-Perfluorophenylazide Methacrylate)

Poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate) wassynthesized as follows: 2 g sulfobetaine methacrylate monomer, 156 mgperfluorophenylazide methacrylamide monomer and 2 g tetrabutylammoniumchloride were dissolved in 30 mL trifluoroethanol in a Schlenk flask andunderwent two vacuum-argon cycles. Then, 14 mg Cu(I)Cl and 76 μL1,1,4,7,10,10-Hexamethyltriethylenetetramine were added. The Schlenkflask was sealed with a rubber septum and another two vacuum-argoncycles were performed. Finally, 44 mg TFA protected 2-aminoethyl2-bromoisobutyrate as ATRP initiator was dissolved in a small amount oftrifluoroethanol (˜0.5 mL) and syringe-injected into the Schlenk flask,followed by two additional vacuum-argon cycles. Polymerization wascarried out at 60° C. under argon protection. After 24 h, the reactionmixture was cooled down to room temperature and the polymer was purifiedby performing membrane dialysis using a membrane with cut off molecularweight of 1000 Dalton. The resulting copolymer was freeze-dried beforefurther use.

NMR spectra were recorded on a Bruker DPX300 spectrometer. Chemicalshifts were calibrated to residual solvent signals. Molecular weightsand dispersities were measured by gel permeation chromatography on aShimadzu HPLC system with a refractive index detector S3 RID-10A, oneTosoh TSKGel guard column, and one Tosoh TSKGel G4000PW column. Eluentwas 0.1 M NaNO₃+20 mM phosphate buffer pH 7+20% MeCN at 25° C. (flowrate 0.7 mL/min). Calibration was performed using near-monodisperse PEGstandards from Polymer Laboratories. Light scattering was used to obtainthe absolute molecular weight.

Example 4. Silicone Surface Modification and Characterization

Poly(sulfobetaine methacrylate-co-perfluorophenylazide methacrylate) wasdissolved or suspended in DI water to prepare 2-20 mg/mL aqueousmixture. Silicone elastomer films were prepared by mixing 10:1 (byweight) base: crosslinker (Sylgard 184), followed by degassing undervacuum and subsequently crosslinking at 70° C. for 8 h. Foranti-biofouling experiments, 2 mg/mL poly(sulfobetainemethacrylate-co-perfluorophenylazide methacrylate) aqueous mixture wasspread onto a cured silicone elastomer surface and exposed to 254 nm UVlight irradiation for 10 mins. Then the silicone elastomer surface wasrinsed with large amounts of DI water to remove unreacted and physicallyadsorbed poly(sulfobetaine methacrylate-co-perfluorophenylazidemethacrylate) molecules from the surface and stored underneath a layerof water before further use.

Contact angles of deionized water (18 MΩ/cm, Millipore) on polymercoatings were measured using a rame-hart Model 590 goniometer. Advancingangles (θ_(adv)) were measured as water was supplied via a syringe,while receding angles (θ_(rec)) were measured as water was removed via asyringe. The total drop volume was 5 μL, and the pump dispensing speedwas 0.2 μL/s. Measurements were taken over three or more differentlocations on each surface, and the reported values are in the format ofaverage±standard deviation.

For surface modification, the following photoreaction takes place.First, PFPA decomposes by releasing N2 to give the singlet phenylnitreneupon activation of the compound by UV light. The singlet phenylnitrenefurther undergoes C—H or N—H insertion, and C═C addition reactions whichcontributes to the covalent bond formation with the target surfaces(Liu, L.-H. et al. Perfluorophenyl azides: new applications in surfacefunctionalization and nanomaterial synthesis. Accounts of ChemicalResearch 2010, 43 (11), 1434-1443). In this process, “the singletphenylnitrene” reaction intermediate is a strong nucleophile and itsstability is not affected by the existence of oxygen and watermolecules.

Example 5. Substrates Modification and Characterization

Coating Substrates with PSB:

PDMS substrates were prepared by mixing a 10:1 ratio of elastomer tocuring agent, followed by curing at 80° C. for 1 h. The PDMS disks werecut with a laser cutter into 3 mm diameter disks. 30 μL of coating (PSB)mixture with concentrations ˜2, 5, or 10 mg mL⁻¹ was placed and spreadout on the surface of each disk. The PSB was then crosslinked on thediscs by exposing them to 254 nm UV light for 10 min under sterileconditions, followed by rinsing with Milli-Q water and drying with air.

Contact Angle Visualization and Measurement:

Water contact angle on various substrates, such as PDMS, Nylon 66,polystyrene, polyvinyl chloride, and polyethylene was visualized byplacing 17 μL of Milli-Q water on the flat substrates at roomtemperature followed by imaging them. The images were analyzed usingFta32 version 2.1 software to measure the contact angle. To study therecovery of water contact angle on PDMS substrates, they were dividedinto two groups: (i) uncoated PDMS sheets, which were treated using 02plasma (Plasma Etch PE25-JW Plasma Cleaner, NV, US) for 1 min, followedby measuring water contact angle after 1, 2, 4, 7, and 10 days, and (ii)PDMS sheets that were coated with PSB, and the contact angle wassimilarly measured over time.

Profilometry:

A calibrated, mechanical 2-D profilometer (Dektak) was used to measurethe roughness of polymer coating on PDMS substrates. The polymer isfirst coated as described above and placed under the measuring platformof the profilometer. A diamond stylus of 25 μm with a stylus angle 90°was traversed in a length of 1.7 mm for 60 s. Three measurements fromone end of the coated polymer to the other end across the diameter wereperformed per sample. The measurements were then analyzed using DektakV9 software to obtain roughness versus distance.

XPS studies were carried out on a Kratos AXIS Ultra DLD with amonochromatic Al Kα X-ray source operating at 10 mA and 15 kV. Surveyspectra and individual high-resolution spectra were collected using passenergies of 160 and 20 eV, respectively. Data processing were performedusing CasaXPS 2.3 software, and spectra binding energies were calibratedby assigning the hydrocarbon peak in the CIs high-resolution spectra to284.6 eV

Cell Culture:

NIH/3T3 fibroblast cells were cultured in cell culture flasks containingDMEM with 10% FBS and 1% P/S and passaged twice a week. For thispurpose, a standard cell culture incubator (Thermo Fisher Scientific,PA, USA) was used to provide 5% CO₂ atmosphere and temperature=37° C. Toconduct cell studies, 0.5% trypsin-EDTA was used to trypsinizefibroblast cells and count them using a hemocytometer, followed byseeding them on desirable substrates.

Cell Adhesion:

Trypsinized fibroblasts cells were seeded on PSB-coated 96-well platesby placing 100 μL of the cell suspension (cell density ˜1×10⁵ in 1 mLmedia) on the treated well plates, cultured for 24 h. Uncoated wellplates were used as a control.

Cytotoxicity Evaluation:

To assess the cytotoxicity of un-crosslinked PSB, trypsinizedfibroblasts cells were seeded on 96-well plates by placing 100 μL of thecell suspension (cell density ˜1×10⁵ in 1 mL media) and cultured for 24h, followed by adding a desired amount of un-crosslinked PSB to themedia and further culturing for 72 h. The cytotoxicity of crosslinkedPSB was evaluated by seeding 500 μL of cell suspension (cell density˜2×10⁵ in 1 mL media) in 24-well plates, culturing for 24 h, followed byplacing PSB coated PDMS discs (diameter ˜6 mm, height ˜3 mm) in themedium and further culturing for 72 h.

Metabolic Activity Assessment:

MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)(Thermo Fisher Scientific) stain solutions were prepared at aconcentration ˜5 mg mL⁴ in DPBS. Cell culture media were removed fromthe well plates, followed by one time rinsing with DPBS. The wells werethen loaded with fresh media and MTT solution at a ratio of 9:1. Thewell plates were wrapped with aluminum foil and incubated for 4 h at 37°C. and 5% CO₂. After 4 h, the wells were aspirated with a pipette and200 or 500 μL of DMSO was added for 96- and 24-well plates,respectively. The well plates were wrapped with aluminum foil again andleft on a rotator for 30 min, after which absorbance was recorded at 570nm using a microplate reader (Synergy HTX multi-mode reader, BioTek, VT,USA).

Live/Dead Assay:

To assess the cell viability, a live/dead fluorescence assay was used.The staining solution was prepared by adding ethidium homodimer-1 (20μL) and calcein AM (5 μL) to DPBS (10 mL). To perform the assay, thecells were incubated with 1 mL of the staining solution forapproximately 20 min and imaged using a fluorescent microscope (AxioObserver 5, Zeiss, Germany) at excitation/emission wavelengths ˜494/515nm for calcein and 528/617 nm for ethidium homodimer-1.

Protein Adsorption:

The protein adsorption was assessed by incubating 100 μg of 50 μg mL⁻¹of Alexa Fluor™ 488 (AF)-conjugated BSA on each PDMS substrate for 1 hat 37° C. To inhibit the photodegradation of AF, aluminum foil was usedto wrap the substrates. Then, the PDMS substrates were gently rinsedwith Milli-Q water and imaged at a constant exposure time ˜1.13 ms usinga fluorescent microscope (Axio Observer 5, Zeiss, Germany) atexcitation/emission wavelengths ˜488/517 nm. ImageJ (National Institutesof Health, US) was used to quantify the emitted fluorescence via themean gray value analysis tool. The average pixel brightness indirectlyreflects the amount of protein adsorbed to the substrates. Backgroundautofluorescence was eliminated using AF-free samples as control.

Bacterial Culture:

Bacterial species, E. coli, S. epidermidis, S. aureus Rosenbach, S.aureus (MRSA), P. aeruginosa, and C. albicans were used in this work.All strains were incubated at 30° C. at 150 rpm until a mid-exponentialphase was reached, at which time the cells were harvested bycentrifugation at 3800×g for 8 min. E. coli was grown on a Luria-Bertani(LB) broth, S. epidermidis, P. aeruginosa, and S. aureus Rosenbach weregrown on nutrient broth; S. aureus (MRSA) was grown on a trypticase soybroth (TSB); and C. albicans was grown on a yeast mold (YM) broth. Theseinitial cultures were then adjusted to an optical density of 1 at 600 nmand had an initial total cell number ranging from 1×10⁷ cells per mL to1×10⁸ cells per mL.

Bacterial Adhesion:

55 mm diameter Petri dishes were filled with a 10:1 elastomer to curingagent (Sylgard 184) and allowed to cure at room temperature for at least48 hours to form a 3 mm thick PDMS film on the bottom of the dishes.Modified plates were coated with a solution containing PFPA-PSB andirradiated with 254 nm UV light. Each modified and unmodified PDMS-lineddish was inoculated with 4 mL of bacterial or fungal suspension andincubated for 24-72 hours (shaken at 25 rpm) at 35° C. The bacterial orfungal suspension was then removed and stored for further microscopy.The Petri dishes were gently rinsed with sterile, deionized water usinga Pasteur pipette, and covered in 4 mL of a dye solution (SYTO 9live/dead Baclight Bacterial Viability Kit L13152, Molecular Probes) for15 min. The SYTO 9 solution was prepared by dissolving the contents ofcomponent A of the kit in 30 mL of sterile, deionized water. After thestaining was complete, the Petri dishes were gently rinsed withdeionized water and imaged using a 4×CCD camera (Axiocam MRm System)attached to a Zeiss Axioskop 2 microscope with a 10× objective, 40×objective, a fluorescent lamp, and a blue excitation filter. Duringobservation, the images were taken at an excitation range of 450-490 nm.The number of attached microorganisms on all fluorescent images weredetermined using ImageJ software.

Statistical analysis: The data were reported as mean values ±standarddeviation of at least triplicate experiments. The one-way analysis ofvariance (ANOVA) and Tukey's multiple comparisons were used, andstatistically significant differences were identified for p-values lowerthan 0.05 (*p<0.05), 0.01 (**p<0.01), 0.001 (***p<0.001), and 0.0001(****p<0.0001).

Example 6. Bacteria Adhesion Test

Escherichia coli was used as the model bacteria for this test. Purebacterial cell cultures were suspended in Luria-Bertani (LB) broth andgrown at 35° C. while being shaken at 150 rpm and incubated until amid-exponential phase was reached, at which time the cells wereharvested by centrifugation at 3800×g for 8 min. The cells were thenre-suspended with fresh LB medium to a concentration of 4×10⁷ cells/mL.Membrane coupons, of approximately 1 cm², were incubated in thisbacterial suspension for 24 hr at 25 rpm and 35° C. The coupons werethen removed from the suspension and gently rinsed with fresh LB brothusing a Pasteur pipette. Once rinsed, the coupons were immersed in a dyesolution (SYTO 9 live/dead Baclight Bacterial Viability Kit L13152,Molecular Probes) for 15 min. The SYTO 9 solution was prepared bydissolving the contents of component A of the kit in 30 mL of steriledistillated water. After the staining was complete, the coupons weregently rinsed with fresh LB broth and imaged using a microscope (OlympusBX51 microscope) equipped with a fluorescent lamp and green/redfluorescence filters and a 4×CCD camera attachment (FVIEW-II, SoftImaging System, USA).

Example 7. Adsorption of BSA on PSB-Modified PDMS Substrates

Assessment of the adsorption of BSA on PSB-modified PDMS substrates andcomparison them with unmodified PDMS was shown. FIG. 6 a presents thefluorescent images of substrates after incubation in Alexa Fluor™ bovineserum albumin (AF-BSA) followed by thorough rinsing with water. For anuncoated PDMS sheet, the adsorption of BSA is evident based on the AFgreen spots. Coating the substrate with PSB significantly decreases thenumber of green spots, and almost no adsorbed protein can be observedwhen the coating is performed from a PSB mixture with a concentration ≥5mg mL⁻¹. The control experiments are the fluorescent images of uncoatedand coated PDMS substrates incubated in milli-Q water, showing no brightspots. The BSA adsorption was quantified by measuring the average pixelbrightness of images, which is shown in FIG. 6 b . Coating thesubstrates with PSB decreases the pixel brightness by a factor of ˜2when PSB coating mixture concentration is 2 mg mL⁻¹, and furtherincreasing the PSB concentration reduces the protein adsorption by morethan 1100%, almost completely eliminating the protein attachment to thesubstrates. The reduction of protein adsorption may be attributed to theformation of a bound water layer at the PSB-medium interfaces,significantly decreasing the electrostatic and hydrophobic interactionsbetween the protein and substrate.

Example 8. Assessment of Cell Adhesion on PSB-Coated Cell Culture WellPlates

The behavior of NIH/3T3 fibroblast cells seeded on PSB-modified cellculture well-plates compared with uncoated wells was explored. Brightfield images of uncoated wells (FIG. 7 a ) show that the cells tend toadhere and spread on the PDMS substrate within a few hours, whereas thePSB-modified wells completely inhibit the cell adhesion, resulting incell detachment and aggregation in the medium. The insets of images showhigh magnification views of the cells for better visualization of theirmorphology. We have also stained the cells using a live/dead assay after24 h of culture to assess their viability. Fibroblast cells cultured onuncoated well-plates and PSB-modified wells were fixed using thelive/dead staining, as shown in FIG. 7 b . While the uncoated wellspermitted the attachment and survival of almost 100% of the cells, thePSB-modified substages prevented cell attachment, yielding cell death.The detached cells were washed off during the staining process. Notethat the negative control includes the cell culture in DMSO, resultingin complete cell death. FIG. 7 c presents the shape factor of cells,measured from 4πA/P², where A is the cell surface area and P is theperimeter, obtained from analyzing at least 20 cells. When the shapefactor is ˜1, the cells adopt a spherical shape, and the elongated cellsrender the shape factor <<1, reaching 0 for a line. The shape factor ofcells cultured on uncoated well plates is approximately 0.2, attestingto an elongated morphology as a result of cell spreading. At a PSBconcentration >2 mg mL⁻¹, the shape factor of cells >0.85, showing anear-spherical morphology. Furthermore, the percentage of cell adheredto the substrate normalized with the seeded cells is presented in FIG. 7d , which shows while the uncoated substrate allows for cellproliferation (reflected in the values >100%), the coated substrates donot support adhesion.

Example 9. Fluorescent Microscopy Images and Quantitative Analysis ofMicrobial Adhesion

Fluorescent microscopy images and quantitative analysis results frommicrobial adhesion after 24-48 hours of incubation on PSB-modified andunmodified surfaces were obtained (FIG. 8 ). Several gram-negative,gram-positive, biofilm forming strains and one fungus were incubateddirectly on bare and PSB coated PDMS sheets and analyzed withfluorescent microscopy. The PSB-modified surfaces exhibit significantdecrease in bacterial and fungal adhesion and biofilm formation comparedto the unmodified surface across all strains. The zwitterionic coatingstrongly binds water electrostatically, preventing adhesion of bacterialsurface proteins that facilitate attachment and activation of thebiofilm forming cascade.

Example 10. Assessment of Protein and Bacterial Adhesion on PSB-CoatedPDMS Microfluidic Channels Under Flow

Microfluidics systems utilizing a PDMS substrate provide a usefulplatform to study the effect of the PSB coating on protein and cellularadhesion under both static and flow conditions. Two sets of experimentswere performed; fluorescent fibrinogen was chosen as a model protein andEscherichia coli containing Green Fluorescent Protein (GFP) was chosenas model bacteria. For these experiments, microfluidic channels of 1 mmdiameter were fabricated. As PDMS is a relatively UV transparentmaterial, the modified channels were obtained by flowing the PSBcontaining mixture into the channel and irradiating with UV light. DIwater was then flowed through the channel to remove any unboundmaterial.

Fluorescent fibrinogen was selected as the model protein for this studydue to its availability and the role of fibrinogen in blood clotting, asdiscussed in the introduction. For both the flow and static experiments,a solution of 10 μg mL fluorescent fibrinogen in DI water was prepared.For the flow experiment (FIG. 9 a ), the microfluidic channels wereplaced under a microscope as the solution was extruded through a syringevia syringe pump at a rate of 10 ul/min. Images were taken at the timethe channels were filled (0 minutes) and every 5 minutes after that withan exposure of 1 s. The increased fluorescence seen in each of theimages compared to the first image of the sequence can be attribute tothe adhesion of the fluorescent fibrinogen to the walls of the channel.The difference between the images of the bare PDMS and PSB-PDMS at 0minutes is due to adhesion of the fluorescent fibrinogen as the channelwas filled. Using ImageJ, the mean gray value representing the averagefluorescent intensity for each image was determined and the percentageincrease relative to the initial (0 Minute) image was calculated. Thebare PDMS fluorescent intensity increased by 138.3%, 217.2%, and 280.3%for the 5, 10, and 15 minute images respectively. For the PSB-PDMScoated channel, there were fluorescent intensity increases of 20.5%,26.5%, and 31.9% for the 5, 10, and 15 minute images respectively. Forthe static adhesion experiment (FIG. 9 b ), the channels were againfilled with the 10 ug/mL solution of fluorescent fibrinogen in DI water.The solution was allowed to sit for 30 minutes before DI water wasflowed through the channel at a rate of 10 ug/mL for 2 minutes to removeany unbound protein. An image was then taken of each channel at anexposure of 500 ms. There is significant adhesion to the bare PDMSchannel and virtually no adhesion to the PSB-PDMS channel.

Example 11. Cytotoxicity of Un-Crosslinked and Crosslinked PSB

The cytotoxicity of PSB before crosslinking was investigated by addingun-crosslinked PSB to the cell culture media and monitoring the behaviorof 2D cultured fibroblast cells within 72 h, as shown schematically inFIG. 10 a . The metabolic activity of cells is quantified based on thereduction of MTT by viable, metabolically active cells, reflected in thefluorescent intensity alteration due to the formation of intracellularpurple formazan. The fluorescent intensity was normalized with thefluorescent intensity obtained from the cells in PSB-free media in days1, 2, and 3, which shows that up to 1.6 mg mL⁻¹ of PSB does not induceany significant decrease in the metabolic activity of cells, i.e., PSBdoes not compromise the cell viability. Staining the cells using thelive/dead assay, presented in FIG. 10 b , shows that the behavior ofcells exposed to un-crosslinked PSB is similar to PSB-free cells, whichall exhibit a 100% viability. The toxicity of crosslinked PSB (coating)was also assessed by coating it on PDMS discs and incubating the discsin the cell culture media of 2D fibroblast cell culture, asschematically shown in FIG. 10 c . The metabolic activity of cellsincubated with the PDMS substrates or PSB-coated PDMS substrates in themedia are identical to the control, attesting to the biosafety of thecoatings. The live/dead staining (FIG. 10 d ) of the fibroblast cellsincubated with the coated PDMS shows no sign of toxicity (dead cells),which further confirms that the crosslinked PSB does not impose anycytotoxicity to the cells. Accordingly, PSB provides a safe platform forcoating substrates, e.g., medical devices, that are directly in contactwith cells.

Example 12. Contact Lens Modification and Characterization

There are over 140 million wearers of contact lenses (CL) worldwide,roughly 50% percent of whom report dryness or discomfort resulting in asmuch as 26% of wearers to discontinue usage of the product within thefirst year. According to a study by Zion Market Research, the contactlens market was valued at 10.91 billion USD in 2017 and is expected togrow at a rate of 7.1% annually through 2024. There is thereforesignificant interest in next generation contact lenses with superiormaterial and surface properties which reduce wearer discomfort.

Hydrogels have become the predominant material of choice for contactlenses due to their high oxygen permeability and wettability. Surfacelubricity, lens hydration, oxygen permeability, and protein/bacterialadhesion are all factors that affect the frequency of contact lensdiscomfort. It has been shown that surface modification of the contactlenses leading to enhanced physical surface properties improves reportedwearer comfort. While several promising surface modifications have beenpresented, most of the surface modification strategies employed requireexpensive chemicals/equipment or extended manufacturing times making itdifficult to scale these processes at the low costs necessary forcontact lenses.

Radical initiated polymerization through methacrylate/methacrylamidelinkages to produce a perfluorophenyl azide-polysulfobetaine (PFPA-PSB)copolymer was used for coating of contact lenses. The copolymer wasmixed with water at different concentrations to make a coating mixture.The contact lenses are immersed in the coating mixture and the coatingis grafted to the surface upon exposure to 254 nm UV light under ambientconditions.

Two forms of modified contact lenses were presented. The first,(PFPA-PSB modified) was simply immersed in a mixture of PFPA-PSB in DIwater at a concentration of 10 mg/mL and subjected to 254 nm UV lightfor 15 minutes. The second, (ethanol treated, PFPA-PSB modified) wassoaked in ethanol for 5 minutes prior to being immersed in the PFPA-PSBmixture and subject to UV light. Three different types of contact lenseswere purchased for this work: Acuve Oasys (two week use), Acuve Moist(one day use), and Acuve Oasys with Hydraluxe (one day use). For eachtype of lens, a control sample, a PFPA-PSB Modified sample, and anethanol treated, PFPA-PSB modified sample were used.

Contact angle measurements were taken using a goniometer and DI water(FIG. 11 ). In all cases, the modified samples exhibit a lower contactangle than the controls indicating that the modification induces a morehydrophilic surface.

A bacterial adhesion test was then performed using Escherichia coli.Contact lens samples were incubated in a solution of Escherichia colifor 24 hours, then rinsed with DI water, stained using a SYTO 9 dyesolution, and then rinsed again to remove any unbound dye. The sampleswere then imaged using a fluorescent microscope at 485 nm with 240millisecond exposure. Three images were taken of each sample and thenumber of fluorescent pixels were quantified using imageJ to obtain aPercent Area Coverage value for each image. These values were averagedfor each sample to obtain an Average Percent Area Coverage Value, whichis presented in FIG. 12 along with one of the images taken for eachsample.

A timed drying experiment was then performed in which the contact lenseswere immersed in DI water for 24 hours and then removed an allowed todry in uncapped scintillation vials. The mass of each contact lens wasrecorded at 0 Minutes, 30 Minutes, 60 Minutes, 120 Minutes, 180 Minutes,240 Minutes, and 300 Minutes. The contacts were then placed in a vacuumchamber overnight to remove any remaining water and obtain the dryweight of each lens. A Water Content value was then obtained bysubtracting the dry weight from the observed weight at each time pointand dividing that value by the observed weight. The results arepresented in FIG. 13 , it is clear in all cases that the modifiedsamples exhibit superior water retention.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the disclosure. It should beunderstood that various alternatives to the embodiments of thedisclosure described herein may be employed in practicing thedisclosure. It is intended that the following claims define the scope ofthe disclosure and that methods and structures within the scope of theseclaims and their equivalents be covered thereby.

NUMBERED EMBODIMENTS

The following embodiments recite nonlimiting permutations ofcombinations of features disclosed herein. Other permutations ofcombinations of features are also contemplated. In particular, each ofthese numbered embodiments is contemplated as depending from or relatingto every previous or subsequent numbered embodiment, independent oftheir order as listed.

Embodiment 1 is a compound that has the structure of Formula (I):

wherein

-   -   A is selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and        —S(═O)(—NR³)—;    -   L is selected from —OQ, —NR³Q, and —N(R³)₂Q⁺;    -   Q is a structure represented by a formula:

-   -   Z is selected from —CR^(6a)R^(6b)—, —C(═O)—, —C(═NH)—, and        —C(═NH)NR⁷—;    -   m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;    -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each R³ is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, —X-optionally substituted C1-C4 alkyl,        optionally substituted aryl, and —X-optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4a), R^(4b), R^(5a), R^(5c), R^(6a), and R^(6b) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted aryl, —NR^(8a)R^(8b),        —NR^(8a)R^(8b)R^(8c+), —S(═O)₂O⁻, —S(═O)₂OR⁹, —C(═O)O⁻, and        —C(═O)OR⁹;    -   R^(5b) is —NR^(10a)R^(10b) or —NR^(10a)R^(10b)R^(10c+);    -   each R⁷, R^(8a), R^(8b), R^(8c), and R⁹ is independently        selected from hydrogen and optionally substituted C1-C4 alkyl,        and optionally substituted aryl;    -   each R^(10a) and R^(10c) is independently selected from        hydrogen, optionally substituted C1-C4 alkyl, optionally        substituted aryl, -(optionally substituted        C1-C8alkylene)S(═O)₂O⁻, -(optionally substituted        C1-C8alkylene)S(═O)₂OH, -(optionally substituted        C1-C8alkylene)C(═O)O—, and -(optionally substituted        C1-C8alkylene)C(═O)OH; and    -   R^(10b) is —(C═O)—C2-C6alkenyl, —(S═O)—C2-C6alkenyl, or        —(S═O)₂—C2-C6alkenyl.

Embodiment 2 is the compound of embodiment 1, wherein the compound has astructure selected from:

Embodiment 3 is the compound of embodiment 1 or 2, wherein the compoundhas a structure selected from:

Embodiment 4 is the compound of any one of embodiments 1-3, wherein thecompound has the following structure:

Embodiment 5 is the compound of embodiment 1, wherein the compound hasthe structure selected from:

Embodiment 6 is the compound of embodiment 1, wherein the compound hasthe following structure:

Embodiment 7 is the compound of embodiment 5 or 6, wherein R^(1a),R^(1b), R^(2a), and R^(2b) are each —F.

Embodiment 8 is the compound of any one of embodiments 1-7, wherein Z is—CR^(6a)R^(6b)—.

Embodiment 9 is the compound of embodiment 8, wherein R^(6a) and R^(6b)are each hydrogen.

Embodiment 10 is the compound of any one of embodiments 1-9, wherein mis 0, 1, 2, or 3.

Embodiment 11 is the compound of embodiment 10, wherein m is 0.

Embodiment 12 is the compound of any one of embodiments 1-11, whereinR^(5a) is hydrogen; R^(5b) is —NR^(10a)R^(10b); and R^(5c) is hydrogen.

Embodiment 13 is the compound of embodiment 1, wherein the compound hasthe structure of Formula (Ia):

Embodiment 14 is the compound of embodiment 1, wherein the compound hasthe structure of Formula (Ib):

Embodiment 15 is the compound of embodiment 13 or 14, wherein R^(10a) ishydrogen.

Embodiment 16 is the compound of any one of embodiments 13-15, whereinR³ is hydrogen.

Embodiment 17 is a compound that has the structure of Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3e)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

Embodiment 18 is the compound of embodiment 17, wherein each R^(1a) andR^(1b) is independently halogen.

Embodiment 19 is the compound of embodiment 17 or 18, wherein eachR^(1a) and R^(1b) is independently F or Cl.

Embodiment 20 is the compound of any one of embodiments 17-19, whereinR^(1a) and R^(1b) are each F.

Embodiment 21 is the compound of any one of embodiments 17-20, whereineach R^(2a) and R^(2b) is independently selected from halogen, —CN, and—CF₃;

Embodiment 22 is the compound of any one of embodiments 17-21, whereineach R^(2a) and R^(2b) is independently selected from F, Cl, —CN, and—CF₃;

Embodiment 23 is the compound of any one of embodiments 17-22, whereinR^(2a) and R^(2b) are each F.

Embodiment 24 is the compound of any one of embodiments 17-23, whereinA¹ is —S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment 25 is the compound of embodiment 24, wherein B¹ and B² areeach —NR^(3c)—.

Embodiment 26 is the compound of embodiment 25, wherein R^(3c) ishydrogen or —CH₃.

Embodiment 27 is the compound of embodiment 26, wherein R^(3c) ishydrogen.

Embodiment 28 is the compound of embodiment 24, wherein B³ is —O—.

Embodiment 29 is the compound of any one of embodiments 17-28, wherein Dis —S(═O)₂OR^(9a) or —C(═O)OR⁹a

Embodiment 30 is the compound of embodiment 29 wherein R^(9a) ishydrogen or —CH₃.

Embodiment 31 is the compound of any one of embodiments 17-28, wherein Dis —S(═O)₂O⁻ or —C(═O)O⁻.

Embodiment 32 is the compound of embodiment 31, wherein D is —S(═O)₂O⁻.

Embodiment 33 is the compound of any one of embodiments 17-32, whereineach R^(6c) and R^(6d) is hydrogen.

Embodiment 34 is the compound of any one of embodiments 17-33, whereineach R^(3a) and R^(3b) is —CH₃.

Embodiment 35 is the compound of any one of embodiments 17-34, whereinR^(11a) is hydrogen or —CH₃.

Embodiment 36 is the compound of embodiment 35, wherein R^(11a) is —CH₃.

Embodiment 37 is the compound of any one of embodiments 17-36, whereinR^(12a) is hydrogen or —CH₃.

Embodiment 38 is the compound of embodiment 37, wherein R^(12a) is —CH₃.

Embodiment 39 is the compound of any one of embodiments 17-38, whereineach R^(11b), R^(11c), R^(12b), and R^(12c) is hydrogen.

Embodiment 40 is a compound that has the structure of Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

Embodiment 41 is the compound of embodiment 40, wherein each R^(1a) andR^(1b) is independently halogen.

Embodiment 42 is the compound of embodiment 40 or 41, wherein eachR^(1a) and R^(1b) is independently F or Cl.

Embodiment 43 is the compound of any one of embodiments 40-42, whereinR^(1a) and R^(1b) are each F.

Embodiment 44 is the compound of any one of embodiments 40-43, whereineach R^(2a) and R^(2b) is independently selected from halogen, —CN, and—CF₃;

Embodiment 45 is the compound of any one of embodiments 40-44, whereineach R^(2a) and R^(2b) is independently selected from F, Cl, —CN, and—CF₃;

Embodiment 46 is the compound of any one of embodiments 40-45, whereinR^(2a) and R^(2b) are each F.

Embodiment 47 is the compound of any one of embodiments 40-46, whereinA¹ is —S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment 48 is the compound of embodiment 47, wherein B¹ and B² areeach —NR^(3c)—.

Embodiment 49 is the compound of embodiment 48, wherein R^(3c) ishydrogen or —CH₃.

Embodiment 50 is the compound of embodiment 49, wherein R^(3c) ishydrogen.

Embodiment 51 is the compound of embodiment 47, wherein B³ is —NR^(3c)—.

Embodiment 52 is the compound of embodiment 51, wherein R^(3c) ishydrogen.

Embodiment 53 is the compound of any one of embodiments 40-52, wherein Eis —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR^(9a).

Embodiment 54 is the compound of embodiment 53, wherein E is—NR^(9a)R^(9b)R^(9c+).

Embodiment 55 is the compound of embodiment 54, wherein each R^(9a),R^(9b), or R^(9c) is H or —CH₃.

Embodiment 56 is the compound of embodiment 55, wherein each R^(9a),R^(9b), or R^(9c) is H.

Embodiment 57 is the compound of embodiment 55, wherein each R^(9a),R^(9b), or R^(9c) is —CH₃.

Embodiment 58 is the compound of embodiment 53, wherein E is—S(═O)₂OR^(9a).

Embodiment 59 is the compound of embodiment 58, wherein R^(9a) H or—CH₃.

Embodiment 60 is the compound of embodiment 59, wherein each R^(9a) isH.

Embodiment 61 is the compound of embodiment 59, wherein each R^(9a) is—CH₃.

Embodiment 62 is the compound of any one of embodiments 40-61, whereineach R^(6c) and R^(6d) is independently selected from hydrogen and —CH₃.

Embodiment 63 is the compound of any one of embodiments 40-62, whereineach R^(3a) and R^(3b) is —CH₃.

Embodiment 64 is the compound of any one of embodiments 40-63, whereinR^(11a) is hydrogen or —CH₃.

Embodiment 65 is the compound of embodiment 64, wherein R^(11a) is —CH₃.

Embodiment 66 is the compound of any one of embodiments 40-65, whereinR^(12a) is hydrogen or —CH₃.

Embodiment 67 is the compound of embodiment 66, wherein R^(12a) is —CH₃.

Embodiment 68 is the compound of any one of embodiments 40-67, whereineach R^(11b), R^(11c), R^(12b), and R^(12c) is hydrogen.

Embodiment 69 is a medical device coated with a compound of any one ofembodiments 1-68.

Embodiment 70 is a biofouling-resistant medical device, wherein asurface of the medical device is coated with a phenyl azide-basedcopolymer having a number-average molecular weight of between about10,000 and about 250,000.

Embodiment 71 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 10,000 and about 20,000.

Embodiment 72 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 10,000 and about 40,000.

Embodiment 73 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 20,000 and about 60,000.

Embodiment 74 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 40,000 and about 100,000.

Embodiment 75 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 80,000 and about 160,000.

Embodiment 76 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 120,000 and about 200,000.

Embodiment 77 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 14,000 and about 21,000.

Embodiment 78 is the biofouling-resistant medical device of embodiment70, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 15,000 and about 18,000.

Embodiment 79 is a biofouling-resistant medical device, wherein asurface of the medical device is coated with a phenyl azide-basedcopolymer having a polydispersity index (PDI) of between about 1 and1.5.

Embodiment 80 is the biofouling-resistant medical device of embodiment79, wherein the PDI is about 1.4, 1.3, 1.2, or 1.1.

Embodiment 81 is the biofouling-resistant medical device of embodiment79, wherein the PDI is about 1.19.

Embodiment 82 is the biofouling-resistant medical device of any one ofembodiments 70-81, wherein the medical device comprises a dentalinstrument or a medical instrument.

Embodiment 83 is the biofouling-resistant medical device of any one ofembodiments 70-82, wherein the medical device comprises an implant, anIV, a prosthesis, a suturing material, a valve, a stent, a catheter, arod, a shunt, a scope, a contact lens, a tubing, a wiring, an electrode,a clip, a fastener, a syringe, a container, or a combination thereof.

Embodiment 84 is the biofouling-resistant medical device of embodiment83, wherein the medical device is a contact lens.

Embodiment 85 is the biofouling-resistant medical device of embodiment83, wherein the medical device is a catheter.

Embodiment 86 is the biofouling-resistant medical device of embodiment85, wherein the catheter is an indwelling catheter.

Embodiment 87 is the biofouling-resistant medical device of embodiment85, wherein the catheter comprises a uretic catheter or a Foleycatheter.

Embodiment 88 is the biofouling-resistant medical device of embodiment83, wherein the medical device is a scope.

Embodiment 89 is the biofouling-resistant medical device of embodiment88, wherein the scope comprises a scope utilized in an image-guidedsurgery.

Embodiment 90 is the biofouling-resistant medical device of embodiment88, wherein the scope comprises a scope utilized in endoscopy orlaparoscopy.

Embodiment 91 is the biofouling-resistant medical device of embodiment82 or 83, wherein the medical device comprises auditory prostheses,artificial larynx, dental implants, mammary implants, penile implants,cranio/facial tendons, tendons, ligaments, menisci, or disks.

Embodiment 92 is the biofouling-resistant medical device of any one ofembodiments 82, 83, or 91, wherein the medical device comprisesartificial bones, artificial joints, or artificial organs.

Embodiment 93 is the biofouling-resistant medical device of embodiment92, wherein the artificial organs comprise artificial pancreas,artificial hearts, artificial limbs, or heart valves.

Embodiment 94 is the biofouling-resistant medical device of any one ofembodiments 70-81, wherein the medical device comprises a bandage or apatch.

Embodiment 95 is the biofouling-resistant medical device of any one ofembodiments 70-94, wherein the copolymer comprises zwitterioniccopolymer.

Embodiment 96 is the biofouling-resistant medical device of embodiment95, wherein the zwitterionic copolymer comprises polysulfobetaine.

Embodiment 97 is the biofouling-resistant medical device of any one ofembodiments 70-97, wherein the biofouling is produced by a bacterium, avirus, and/or a fungus.

Embodiment 98 is a method of preparing a biofouling-resistant medicaldevice, comprising:

-   -   a) contacting a surface of a medical device with a mixture        comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the medical device of step a) with a        light source for a time sufficient to undergo photografting of        the charged or zwitterion copolymer onto the surface of the        medical device, thereby making the biofouling-resistant medical        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer having a number-average molecular weight of between        about 10,000 and about 250,000.

Embodiment 99 is a method of preparing a charged or zwitterion copolymermodified biofouling-resistant device comprising:

-   -   a) contacting a surface of a silicon-based device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the        silicon-based device, thereby generating the charged or        zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer.

Embodiment 100 is a method of preparing a charged or zwitterioncopolymer modified biofouling-resistant device comprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer having a number-average molecular weight of between        about 10,000 and about 250,000.

Embodiment 101 is the method of any one of embodiments 98-100, whereinthe time sufficient to undergo photografting is at least 1 minute, atleast 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes,8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes or30 minutes.

Embodiment 102 is the method of any one of embodiments 98-101, whereinthe light source is an ultraviolet light source.

Embodiment 103 is the method of embodiment 102, wherein the ultravioletlight source has an intensity of at least 900 μW/cm².

Embodiment 104 is the method of embodiment 102 or 103, wherein theultraviolet light source has a wavelength of between 240 nm and 280 nm,between 240 nm and 275 nm, between 240 nm and 270 nm, between 240 nm and265 nm, between 240 nm and 260 nm, between 240 nm and 255 nm, between240 nm and 250 nm, between 240 nm and 245 nm, between 250 nm and 280 nm,between 250 nm and 275 nm, between 250 nm and 270 nm, between 250 nm and265 nm, between 250 nm and 260 nm, between 255 nm and 280 nm, between255 nm and 275 nm, between 255 nm and 270 nm, between 255 nm and 265 nm,between 255 nm and 260 nm, between 260 nm and 280 nm, between 260 nm and275 nm, between 260 nm and 270 nm, or between 270 nm and 280 nm.

Embodiment 105 is the method of embodiment 102 or 103, wherein theultraviolet light source has a wavelength of at least 240 nm, 245 nm,250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm,259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm,268 nm, 269 nm, 270 nm, 275 nm or 280 nm.

Embodiment 106 is the method of any one of embodiments 98-100, whereinthe mixture of step a) is an aqueous solution, an aqueous colloid, or anaqueous suspension.

Embodiment 107 is the method of any one of embodiments 98-100, whereinphotografting of step b) is not affected by the presence of oxygen.

Embodiment 108 is the method of any one of embodiments 98-107, whereinthe charged or zwitterion copolymer is a compound of any one ofembodiments 17-68.

Embodiment 109 is the method of any one of the embodiments 98-108,wherein the mixture comprising a charged or zwitterion copolymer has aconcentration of the charged or zwitterion copolymer in the mixturebetween 1 mg/mL and 30 mg/mL.

Embodiment 110 is the method of embodiment 109, wherein theconcentration of the charged or zwitterion copolymer in the mixture isbetween 1 mg/mL and 25 mg/mL, between 1 mg/mL and 20 mg/mL, between 1mg/mL and 15 mg/mL, between 1 mg/mL and 10 mg/mL, between 1 mg/mL and 5mg/mL, between 5 mg/mL and 30 mg/mL, between 5 mg/mL and 25 mg/mL,between 5 mg/mL and 20 mg/mL, between 5 mg/mL and 15 mg/mL, between 5mg/mL and 10 mg/mL, between 10 mg/mL and 30 mg/mL, between 10 mg/mL and25 mg/mL, between 10 mg/mL and 20 mg/mL, between 10 mg/mL and 15 mg/mL,between 15 mg/mL and 30 mg/mL, between 15 mg/mL and 25 mg/mL, between 15mg/mL and 20 mg/mL, between 20 mg/mL and 30 mg/mL, or between 20 mg/mLand 25 mg/mL.

Embodiment 111 is the method of embodiment 109, wherein theconcentration of the charged or zwitterion copolymer in the mixture isabout 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15mg/mL, 16 mg/mL, 17 mg/mL, 18 mg/mL, 19 mg/mL, 20 mg/mL, 21 mg/mL, 22mg/mL, 23 mg/mL, 24 mg/mL, 25 mg/mL, 26 mg/mL, 27 mg/mL, 28 mg/mL, 29mg/mL, or 30 mg/mL.

Embodiment 112 is the method of any one of embodiments 98-111, whereinthe concentration of the charged or zwitterion copolymer is between 0.1to 1 mg per square centimeter of the device.

Embodiment 113 is the method of embodiment 99, wherein the charged orzwitterion copolymer has a number-average molecular weight of betweenabout 10,000 and about 250,000

Embodiment 114 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 10,000 and about 20,000.

Embodiment 115 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 10,000 and about 40,000.

Embodiment 116 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 20,000 and about 60,000.

Embodiment 117 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 40,000 and about 100,000.

Embodiment 118 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 80,000 and about 160,000.

Embodiment 119 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 120,000 and about 200,000.

Embodiment 120 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 14,000 and about 21,000.

Embodiment 121 is the method of any one of embodiments 98 or 100-113,wherein the charged or zwitterion copolymer has a number-averagemolecular weight of between about 15,000 and about 18,000.

Embodiment 122 is the method of embodiment 98 or 100, wherein the devicecomprises a carbon-based device or a silicon-based device.

Embodiment 123 is the method of embodiment 122, wherein the devicecomprises a silicon-based device.

Embodiment 124 is the method of embodiment 99 or 123, wherein thesilicon-based device comprises a silicon-based polymer moiety.

Embodiment 125 is the method of embodiment 124, wherein thesilicon-based polymer moiety comprises siloxane polymer moiety,sesquisiloxane polymer moiety, siloxane-silarylene polymer moiety,silalkylene polymer moiety, polysilane moiety, polysilylene moiety, orpolysilazane moiety.

Embodiment 126 is the method of embodiment 101, wherein thesilicon-based device comprises siloxane polymer moiety.

Embodiment 127 is the method of embodiment 98, wherein the devicecomprises a carbon-based device.

Embodiment 128 is the method of embodiment 127, wherein the carbon-baseddevice comprises a carbon-based polymer.

Embodiment 129 is the method of embodiment 127, wherein the carbon-baseddevice comprises a polyolefin moiety.

Embodiment 130 is the method of embodiment 129, wherein the polyolefinmoiety comprises polyethylene moiety, polypropylene moiety, polyvinylchloride moiety, polyvinylidene fluoride moiety, polytetrafluoroethylenemoiety, polychlorotrifluoroethylene moiety, or polystyrene moiety.

Embodiment 131 is the method of embodiment 128, wherein the carbon-basedpolymer comprises polyamide moiety, polyurethane moiety,phenol-formaldehyde resin moiety, polycarbonate moiety, polychloroprenemoiety, polyacrylonitrile moiety, polimide moiety, or polyester moiety.

Embodiment 132 is the method of embodiment 128, wherein the carbon-basedpolymer comprises nylon.

Embodiment 133 is the method of embodiment 128, wherein the carbon-basedpolymer comprises polyethylene terephthalate.

Embodiment 134 is the method of any one of embodiments 98-133, whereinthe copolymer comprises zwitterionic copolymer.

Embodiment 135 is the method of embodiment 134, wherein the zwitterioniccopolymer comprises polysulfobetaine.

Embodiment 136 is the method of any one of embodiments 98-135, whereinthe biofouling is produced by a bacterium, a virus, and/or a fungus.

Embodiment 137 is a method for synthesizing a compound of Formula (II)comprising: reacting a compound of Formula (IV) or a salt or solvatethereof with a compound of Formula (V):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) and Formula (V) are each        independently charged or zwitterionic.

Embodiment 138 is the method of embodiment 137, wherein each R^(1a) andR^(1b) is independently halogen.

Embodiment 139 is the method of embodiment 137 or 138, wherein eachR^(1a) and R^(1b) is independently F or Cl.

Embodiment 140 is the method of any one of embodiments 137-139, whereinR^(1a) and R^(1b) are each F.

Embodiment 141 is the method of any one of embodiments 137-140, whereineach R^(2a) and R^(2b) is independently selected from halogen, —CN, and—CF₃;

Embodiment 142 is the method of any one of embodiments 137-141, whereineach R^(2a) and R^(2b) is independently selected from F, Cl, —CN, and—CF₃;

Embodiment 143 is the method of any one of embodiments 137-142, whereinR^(2a) and R^(2b) are each F.

Embodiment 144 is the method of any one of embodiments 137-143, whereinA¹ is —S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment 145 is the method of embodiment 144, wherein B¹ and B² areeach —NR^(3c)—.

Embodiment 146 is the method of embodiment 145, wherein R^(3c) ishydrogen or —CH₃.

Embodiment 147 is the method of embodiment 146, wherein R^(3c) ishydrogen.

Embodiment 148 is the method of embodiment 144, wherein B³ is —O—.

Embodiment 149 is the method of any one of embodiments 137-148, whereinD is —S(═O)₂OR^(9a) or —C(═O)OR⁹a

Embodiment 150 is the method of embodiment 149, wherein R^(9a) ishydrogen or —CH₃.

Embodiment 151 is the method of any one of embodiments 137-148, whereinD is —S(═O)₂O⁻ or —C(═O)O⁻.

Embodiment 152 is the method of embodiment 151, wherein D is —S(═O)₂O⁻.

Embodiment 153 is the method of any one of embodiments 137-152, whereineach R^(6c) and R^(6d) is hydrogen.

Embodiment 154 is the method of any one of embodiments 137-153, whereineach R^(3a) and R^(3b) is —CH₃.

Embodiment 155 is the method of any one of embodiments 137-154, whereinR^(11a) is hydrogen or —CH₃.

Embodiment 156 is the method of embodiment 155, wherein R^(11a) is —CH₃.

Embodiment 157 is the method of any one of embodiments 137-156, whereinR^(12a) is hydrogen or —CH₃.

Embodiment 158 is the method of embodiment 157, wherein R^(12a) is —CH₃.

Embodiment 159 is the method of any one of embodiments 137-158, whereineach Rib, R^(11c), R^(12b), and R^(12c) is hydrogen.

Embodiment 160 is a method for synthesizing a compound of Formula (III)comprising: reacting a compound of Formula (IV) or a salt or solvatethereof with a compound of Formula (VI):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4e), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

Embodiment 161 is the method of embodiment 160, wherein each R^(1a) andR^(1b) is independently halogen.

Embodiment 162 is the method of embodiment 160 or 161, wherein eachR^(1a) and R^(1b) is independently F or Cl.

Embodiment 163 is the method of any one of embodiments 160-162, whereinR^(1a) and R^(1b) are each F.

Embodiment 164 is the method of any one of embodiments 160-163, whereineach R^(2a) and R^(2b) is independently selected from halogen, —CN, and—CF₃;

Embodiment 165 is the method of any one of embodiments 160-164, whereineach R^(2a) and R^(2b) is independently selected from F, Cl, —CN, and—CF₃;

Embodiment 166 is the method of any one of embodiments 160-165, whereinR^(2a) and R^(2b) are each F.

Embodiment 167 is the method of any one of embodiments 160-166, whereinA¹ is —S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment 168 is the method of embodiment 167, wherein B¹ and B² areeach —NR^(3c)—.

Embodiment 169 is the method of embodiment 168 wherein R^(3c) ishydrogen or —CH₃.

Embodiment 170 is the method of embodiment 169, wherein R^(3c) ishydrogen.

Embodiment 171 is the method of embodiment 170, wherein B³ is —NR^(3c)—.

Embodiment 172 is the method of embodiment 171, wherein R^(3c) ishydrogen.

Embodiment 173 is the method of any one of embodiments 160-172, whereinE is —NR^(9a)R^(9b)R^(9c+) or —S(═O)₂OR^(9a).

Embodiment 174 is the method of embodiment 173, wherein E is—NR^(9a)R^(9b)R^(9c+).

Embodiment 175 is the method of embodiment 174, wherein each R^(9a),R^(9b), or R^(9c) is H or —CH₃.

Embodiment 176 is the method of embodiment 175, wherein each R^(9a),R^(9b), or R^(9c) is H.

Embodiment 177 is the method of embodiment 175, wherein each R^(9a),R^(9b), or R^(9c) is —CH₃.

Embodiment 178 is the method of embodiment 173, wherein E is—S(═O)₂OR^(9a)

Embodiment 179 is the method of embodiment 178, wherein R^(9a) H or—CH₃.

Embodiment 180 is the method of embodiment 179, wherein each R^(9a) isH.

Embodiment 181 is the method of embodiment 179, wherein each R^(9a) is—CH₃.

Embodiment 182 is the method of any one of embodiments 160-181, whereineach R^(6c) and R^(6d) is independently selected from hydrogen and —CH₃.

Embodiment 183 is the method of any one of embodiments 160-182, whereineach R^(3a) and R^(3b) is —CH₃.

Embodiment 184 is the method of any one of embodiments 160-183, whereinR^(11a) is hydrogen or —CH₃.

Embodiment 185 is the method of embodiment 184, wherein R^(11a) is —CH₃.

Embodiment 186 is the method of any one of embodiments 160-185, whereinR^(12a) is hydrogen or —CH₃.

Embodiment 187 is the method of embodiment 186, wherein R^(12a) is —CH₃.

Embodiment 188 is the method of any one of embodiments 160-187, whereineach Rib, R^(11c), R^(12b), and R^(12c) is hydrogen.

Embodiment 189 is a charged or zwitterion copolymer modifiedbiofouling-resistant device prepared by the method comprising:

-   -   a) contacting a surface of a silicon-based device with a mixture        (e.g., a solution) comprising a charged or zwitterion copolymer;        and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the        silicon-based device, thereby generating the charged or        zwitterion copolymer modified device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer.

Embodiment 190 is a charged or zwitterion copolymer modifiedbiofouling-resistant device prepared by the method comprising:

-   -   a) contacting a surface of a device with a mixture (e.g., a        solution) comprising a charged or zwitterion copolymer; and    -   b) treating the surface of the device of step a) with a light        source for a time sufficient to undergo photografting of the        charged or zwitterion copolymer onto the surface of the device,        thereby generating the charged or zwitterion copolymer modified        device;    -   wherein the charged or zwitterion copolymer comprises a phenyl        azide-based copolymer; and wherein the charged or zwitterion        copolymer having a number-average molecular weight of between        about 10,000 and about 250,000.

Embodiment 191 is the device of embodiment 189 or 190, wherein the timesufficient to undergo photografting is at least 1 minute, at least 2minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes or 30minutes.

Embodiment 192 is the device of any one of embodiments 189-191, whereinthe light source is an ultraviolet light source.

Embodiment 193 is the device of embodiment 192, wherein the ultravioletlight source has an intensity of at least 900 μW/cm².

Embodiment 194 is the device of embodiment 192 or 193, wherein theultraviolet light source has a wavelength of between 240 nm and 280 nm,between 240 nm and 275 nm, between 240 nm and 270 nm, between 240 nm and265 nm, between 240 nm and 260 nm, between 240 nm and 255 nm, between240 nm and 250 nm, between 240 nm and 245 nm, between 250 nm and 280 nm,between 250 nm and 275 nm, between 250 nm and 270 nm, between 250 nm and265 nm, between 250 nm and 260 nm, between 255 nm and 280 nm, between255 nm and 275 nm, between 255 nm and 270 nm, between 255 nm and 265 nm,between 255 nm and 260 nm, between 260 nm and 280 nm, between 260 nm and275 nm, between 260 nm and 270 nm, or between 270 nm and 280 nm.

Embodiment 195 is the device of embodiment 192 or 193, wherein theultraviolet light source has a wavelength of at least 240 nm, 245 nm,250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm,259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm,268 nm, 269 nm, 270 nm, 275 nm or 280 nm.

Embodiment 196 is the device of embodiment 189 or 190, wherein themixture of step a) is an aqueous solution, an aqueous colloid, or anaqueous suspension.

Embodiment 197 is the device of embodiment 189 or 190, whereinphotografting of step b) is not affected by the presence of oxygen.

Embodiment 198 is the device of any one of embodiments 189-197, whereinthe charged or zwitterion compound is a compound of any one ofembodiments 1-68.

Embodiment 199 is the device of any one of the embodiments 189-198,wherein the mixture comprising a charged or zwitterion compound has aconcentration of the charged or zwitterion compound in the mixturebetween 1 mg/mL and 30 mg/mL.

Embodiment 200 is the device of embodiment 199, wherein theconcentration of the charged or zwitterion compound in the mixture isbetween 1 mg/mL and 25 mg/mL, between 1 mg/mL and 20 mg/mL, between 1mg/mL and 15 mg/mL, between 1 mg/mL and 10 mg/mL, between 1 mg/mL and 5mg/mL, between 5 mg/mL and 30 mg/mL, between 5 mg/mL and 25 mg/mL,between 5 mg/mL and 20 mg/mL, between 5 mg/mL and 15 mg/mL, between 5mg/mL and 10 mg/mL, between 10 mg/mL and 30 mg/mL, between 10 mg/mL and25 mg/mL, between 10 mg/mL and 20 mg/mL, between 10 mg/mL and 15 mg/mL,between 15 mg/mL and 30 mg/mL, between 15 mg/mL and 25 mg/mL, between 15mg/mL and 20 mg/mL, between 20 mg/mL and 30 mg/mL, or between 20 mg/mLand 25 mg/mL.

Embodiment 201 is the device of embodiment 199, wherein theconcentration of the charged or zwitterion compound in the mixture isabout 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15mg/mL, 16 mg/mL, 17 mg/mL, 18 mg/mL, 19 mg/mL, 20 mg/mL, 21 mg/mL, 22mg/mL, 23 mg/mL, 24 mg/mL, 25 mg/mL, 26 mg/mL, 27 mg/mL, 28 mg/mL, 29mg/mL, or 30 mg/mL.

Embodiment 202 is the device of any one of embodiments 189-201, whereinthe concentration of the charged or zwitterion compound is between 0.1to 1 mg per square centimeter of the device.

Embodiment 203 is the device of embodiment 189, wherein the charged orzwitterion copolymer has a number-average molecular weight of betweenabout 10,000 and about 250,000

Embodiment 204 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 10,000 and about 20,000.

Embodiment 205 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 10,000 and about 40,000.

Embodiment 206 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 20,000 and about 60,000.

Embodiment 207 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 40,000 and about 100,000.

Embodiment 208 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 80,000 and about 160,000.

Embodiment 209 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 120,000 and about 200,000.

Embodiment 210 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 14,000 and about 21,000.

Embodiment 211 is the device of any one of embodiments 190-202, whereinthe charged or zwitterion copolymer has a number-average molecularweight of between about 15,000 and about 18,000.

Embodiment 212 is the device of embodiment 190, wherein the devicecomprises a carbon-based device or a silicon-based device containing amoiety capable of binding with the phenyl azide-zwitterion copolymer ofany one of embodiments 17-68.

Embodiment 213 is the device of embodiment 212, wherein the devicecomprises a silicon-based device.

Embodiment 214 is the device of embodiment 189 or 213, wherein thesilicon-based device comprises a polymer moiety.

Embodiment 215 is the device of embodiment 214, wherein thesilicon-based device comprises a siloxane polymer moiety, asesquisiloxane polymer moiety optionally having a ladder structure, asiloxane-silarylene polymer moiety, a silalkylene polymer moiety, apolysilane moiety, a polysilylene moiety, or a polysilazane moiety.

Embodiment 216 is the device of embodiment 215, wherein thesilicon-based device comprises a siloxane polymer moiety.

Embodiment 217 is the device of embodiment 212, wherein the devicecomprises a carbon-based device.

Embodiment 218 is the device of embodiment 217, wherein the carbon-baseddevice comprises a carbon-based polymer.

Embodiment 219 is the device of embodiment 217, wherein the carbon-baseddevice comprises a polyolefin moiety.

Embodiment 220 is the device of embodiment 219, wherein the polyolefinmoiety comprises polyethylene moiety, polypropylene moiety, polyvinylchloride moiety, polyvinylidene fluoride moiety, polytetrafluoroethylenemoiety, polychlorotrifluoroethylene moiety, or polystyrene moiety.

Embodiment 221 is the device of embodiment 218, wherein the carbon-basedpolymer comprises polyamide moiety, polyurethane moiety,phenol-formaldehyde resin moiety, polycarbonate moiety, polychloroprenemoiety, polyacrylonitrile moiety, polimide moiety, or polyester moiety.

Embodiment 222 is the device of embodiment 218, wherein the carbon-basedpolymer comprises nylon.

Embodiment 223 is the device of embodiment 218, wherein the carbon-basedpolymer comprises polyethylene terephthalate.

Embodiment 224 is the device of any one of embodiments 189-223, whereinthe device is resistant to fouling.

Embodiment 225 is the device of embodiment 224, wherein the deviceprevents and/or reduces biofouling.

Embodiment 226 is the device of embodiment 225, wherein biofoulingcomprises microfouling or macrofouling.

Embodiment 227 is the device of embodiment 226, wherein microfoulingcomprises biofilm and bacterial adhesion.

Embodiment 228 is the device of embodiment 226 or 227, whereinmicrofouling is formed by a bacterium or a fungus.

Embodiment 229 is the device of any one of embodiments 226-228, whereinmicrofouling is formed by a gram-positive bacterium.

Embodiment 230 is the device of embodiment 229, wherein thegram-positive bacterium comprises a bacterium from the genusActinomyces, Arthrobacter, Bacillus, Clostridium, Corynebacterium,Enterococcus, Lactococcus, Listeria, Micrococcus, Mycobacterium,Staphylococcus, or Streptococcus.

Embodiment 231 is the device of embodiment 229 or 230, wherein thegram-positive bacterium comprises Actinomyces spp., Arthrobacter spp.,Bacillus licheniformis, Clostridium difficile, Clostridium spp.,Corynebacterium spp., Enterococcus faecalis, Lactococcus spp., Listeriamonocytogenes, Micrococcus spp., Mycobacterium spp., Staphylococcusaureus, Staphylococcus epidermidis, Streptococcus pneumoniae, orStreptococcus pyogenes.

Embodiment 232 is the device of any one of embodiments 226-228, whereinmicrofouling is formed by a gram-negative bacterium.

Embodiment 233 is the device of embodiment 232, wherein thegram-negative bacterium comprises a bacterium from the genusAlteromonas, Aeromonas, Desulfovibrio, Escherichia, Fusobacterium,Geobacter, Haemophilus, Klebsiella, Legionella, Porphyromonas, Proteus,Pseudomonas, Serratia, Shigella, Salmonella, or Vibrio.

Embodiment 234 is the device of embodiment 232 or 233, wherein thegram-negative bacterium comprises Alteromonas spp., Aeromonas spp.,Desulfovibrio spp., Escherichia coli, Fusobacterium nucleatum, Geobacterspp., Haemophilus spp., Klebsiella spp., Legionella pneumophila,Porphyromonas spp., Pseudomonas aeruginosa, Proteus vulgaris, Proteusmirabilis, Proteus penneri, Serratia spp., Shigella dysenteriae,Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella bongori,Salmonella enterica, or Vibrio Cholerae.

Embodiment 235 is the device of any one of embodiments 226-228, whereinthe bacterium is a marine bacterium.

Embodiment 236 is the device of embodiment 235, wherein the marinebacterium comprises Pseudoalteromonas spp. or Shewanella spp.

Embodiment 237 is the device of any one of embodiments 226-228, whereinmicrofouling is formed by a fungus.

Embodiment 238 is the device of embodiment 237, wherein the funguscomprises Candida albicans, Candida glabrata, Candida rugose, Candidaparapsilosis, Candida tropicalis, Candida dubliniensis, or Hormoconisresinae.

Embodiment 239 is the device of embodiment 226, wherein macrofoulingcomprises calcareous fouling organism or non-calcareous foulingorganism.

Embodiment 240 is the device of embodiment 239, wherein calcareousfouling organism comprises barnacle, bryozoan, mollusk, polychaete, tubeworm, or zebra mussel.

Embodiment 241 is the device of embodiment 239, wherein non-calcareousfouling organism comprises seaweed, hydroids, or algae.

Embodiment 242 is the device of any one of embodiments 189-241, whereinthe formation of biofouling on a surface of a device is reduced by about10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, ormore relative to unmodified surface of a device.

Embodiment 243 is the device of any one of embodiments 189-242, whereinthe device is further coated with an additional agent.

Embodiment 244 is the device of embodiment 243, wherein the additionalagent is an antimicrobial agent.

Embodiment 245 is the device of embodiment 243, wherein the additionalagent is a chemical disinfectant.

Embodiment I is a compound that has the structure of Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

Embodiment II is the compound of embodiment I, wherein each R^(1a) andR^(1b) is independently halogen.

Embodiment III is the compound of embodiment I, wherein each R^(2a) andR^(2b) is independently selected from halogen, —CN, and —CF₃;

Embodiment IV is the compound of embodiment I, wherein A¹ is —S(═O)₂—;A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment V is the compound of embodiment IV, wherein B¹ and B² areeach —NR^(3c)— and wherein B³ is —O—.

Embodiment VI is the compound of embodiment V, wherein D is —S(═O)₂O⁻.

Embodiment VII is the compound of embodiment I, wherein each R^(6c) andR^(6d) is hydrogen and wherein each R^(3a) and R^(3b) is —CH₃.

Embodiment VIII is a compound that has the structure of Formula (III):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   E is —CN, —OR^(9a), —NR^(9a)R^(9b), —NR^(9a)R^(9b)R^(9c+),        optionally substituted C1-C4 alkyl, optionally substituted        C1-C6fluoroalkyl, —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or        —C(═O)OR^(9a);    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OR^(9a),        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60; and    -   r is an integer selected from 1-10.

Embodiment IX is the compound of embodiment VIII, wherein each R^(1a)and R^(1b) is independently halogen.

Embodiment X is the compound of embodiment VIII, wherein each R^(2a) andR^(2b) is independently selected from halogen, —CN, and —CF₃;

Embodiment XI is the compound of embodiment VIII, wherein A¹ is—S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment XII is the compound of embodiment XI, wherein B¹ and B² areeach —NR^(3c)— and wherein B³ is —NR^(3c)—.

Embodiment XIII is the compound of embodiment XII, wherein E is—NR^(9a)R^(9b)R^(9c+).

Embodiment XIV is the compound of embodiment XIII, wherein each R^(9a),R^(9b), or R^(9c+) is H or —CH₃.

Embodiment XV is a medical device coated with a compound that has thestructure of Formula (II):

wherein

-   -   each R^(1a) and R^(1b) is independently selected from hydrogen        and halogen;    -   each R^(2a) and R^(2b) is independently selected from halogen,        —CN, and optionally substituted C1-C6fluoroalkyl;    -   each A¹, A², and A³ is independently selected from —C(═O)—,        —S(═O)—, —S(═O)₂—, and —S(═O)(═NR^(3c))—;    -   each B¹, B², and B³ is independently selected from —O— and        —NR^(3c)—;    -   D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or —C(═O)OR^(9a);    -   Z¹ is —(CR^(6c)R^(6d))_(s)—;    -   Z² is —(CR^(6c)R^(6d))_(t)—;    -   Z³ is —(CR^(6c)R^(6d))_(p)—;    -   each R^(3a) and R^(3b) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, and optionally substituted        benzyl;    -   each R^(3c) and R^(3d) is independently selected from hydrogen,        optionally substituted C1-C4 alkyl, —X-optionally substituted        C1-C4 alkyl, optionally substituted C2-C6 alkenyl, and        optionally substituted aryl;    -   X is —C(═O)—, —S(═O)—, or —S(═O)₂—;    -   each R^(4c), R^(4d), R^(5d), R^(5e), R^(6c), and R^(6d) is        independently selected from hydrogen, halogen, —CN, —OH,        optionally substituted C1-C4 alkyl, optionally substituted C1-C4        fluoroalkyl, optionally substituted C2-C6 alkenyl,        —NR^(3c)R^(3d), —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, and        —C(═O)OR^(9a);    -   each R^(9a), R^(11a), R^(11b), R^(11c), R^(12a), R^(12b), and        R^(12c) is independently selected from hydrogen, optionally        substituted C1-C4 alkyl, and optionally substituted aryl;    -   n is an integer selected from 0, 1, 2, 3, 4, 5, and 6;    -   s is an integer selected from 1, 2, 3, 4, or 5;    -   t is an integer selected from 1, 2, 3, 4, or 5;    -   p is an integer selected from 1, 2, 3, 4, or 5;    -   q is an integer selected from 40-60;    -   r is an integer selected from 1-10; and    -   wherein the compounds of Formula (II) is charged or        zwitterionic.

Embodiment XVI is the medical device of embodiment XV, wherein eachR^(1a) and R^(1b) is independently halogen.

Embodiment XVII is the medical device of embodiment XV, wherein eachR^(2a) and R^(2b) is independently selected from halogen, —CN, and —CF₃;

Embodiment XVIII is the medical device of embodiment XV, wherein A¹ is—S(═O)₂—; A² is —C(═O)—; and A³ is —C(═O)—.

Embodiment XIX is the medical device of embodiment XVIII, wherein B¹ andB² are each —NR^(3c)— and wherein B³ is —O—.

Embodiment XX is the medical device of embodiment XIX, wherein D is—S(═O)₂O⁻.

Embodiment XXI is the medical device of embodiment XV, wherein eachR^(6c) and R^(6d) is hydrogen and wherein each R^(3a) and R^(3b) is—CH₃.

Embodiment XXII is the medical device of embodiment XV, wherein themedical device comprises an implant, an IV, a prosthesis, a suturingmaterial, a valve, a stent, a catheter, a rod, a shunt, a scope, acontact lens, a tubing, a wiring, an electrode, a clip, a fastener, asyringe, a container, or a combination thereof.

Embodiment XXIII is a biofouling-resistant medical device, wherein asurface of the medical device is coated with a phenyl azide-basedcopolymer that has a number-average molecular weight of between about10,000 and about 250,000.

Embodiment XXIV is the biofouling-resistant medical device of embodimentXXIII, wherein the phenyl azide-based copolymer has a number-averagemolecular weight of between about 10,000 and about 20,000.

Embodiment XXV is the biofouling-resistant medical device of embodimentXXIII, wherein the phenyl azide-based copolymer has a polydispersityindex (PDI) of between about 1 and 1.5.

Embodiment XXVI is the biofouling-resistant medical device of embodimentXXIII, wherein the medical device comprises an implant, an IV, aprosthesis, a suturing material, a valve, a stent, a catheter, a rod, ashunt, a scope, a contact lens, a tubing, a wiring, an electrode, aclip, a fastener, a syringe, a container, or a combination thereof.

Embodiment XXVII is the biofouling-resistant medical device ofembodiment XXVI, wherein the medical device is a catheter.

Embodiment XXVIII is the biofouling-resistant medical device ofembodiment XXVII, wherein the catheter is an indwelling catheter.

Embodiment XXIX is the biofouling-resistant medical device of embodimentXXIII, wherein the copolymer comprises polysulfobetaine.

Embodiment XXX is the biofouling-resistant medical device of embodimentXXIII, wherein the biofouling is produced by a bacterium, a virus,and/or a fungus.

1.-30. (canceled)
 31. A compound comprising a phenyl azide monomerhaving the structure of formula (IV):

and a zwitterionic monomer having the structure of formula (V):

wherein each R^(1a) and R^(1b) is independently selected from hydrogenand halogen; each R^(2a) and R^(2b) is independently selected fromhalogen, CN, and optionally substituted C₁-C₆ fluoroalkyl; each A¹, A²,and A³ is independently selected from —C(═O)—, —S(═O)—, —S(═O)₂—, and—S(═O)(═NR^(3c))—; each B¹, B², and B³ is independently selected from—O— and —NR^(3c)—; D is —S(═O)₂O⁻, —S(═O)₂OR^(9a), —C(═O)O⁻, or—C(═O)R^(9a); Z¹ is —(CR^(6c)R^(6d))_(s)—; Z² is —(CR^(6c)R^(6d))_(t)—;Z³ is —(CR^(6c)R^(6d))_(p)—; each R^(3a) and R^(3b) is independentlyselected from hydrogen, optionally substituted C₁-C₄ alkyl, andoptionally substituted benzyl; each R^(3c) and R^(3d) is independentlyselected from hydrogen, optionally substituted C₁-C₄ alkyl, X—,optionally substituted C₁-C₄ alkyl, optionally substituted C₂-C₆alkenyl, and optionally substituted aryl; each R^(4c), R^(4d), R^(5d),R^(5c), R^(6c) and R^(6d) is independently selected from hydrogen,halogen, CN, OR^(9a), optionally substituted C₁-C₄ alkyl, optionallysubstituted C₁-C₄ fluoroalkyl, optionally substituted C₂-C₆ alkenyl,—NR^(3c)R^(3d), —S(═O)₂O—, —S(═O)₂OR^(9a), —C(═O)O—, and —C(═O)OR^(9a);X is —C(═O)—, —S(═O)—, or —S(═O)₂—; each R^(9a), R^(11a), R^(11b),R^(11c), R^(12a), R^(12b) and R^(12c) is independently selected fromhydrogen, optionally substituted C₁-C₄ alkyl, and optionally substitutedaryl; n is an integer selected from 0, 1, 2, 3, 4, 5, or 6; s is aninteger selected from 1, 2, 3, 4, or 5; t is an integer selected from 1,2, 3, 4, or 5; and p is an integer selected from 1, 2, 3, 4, or
 5. 32.The compound of claim 31, wherein R^(1a) and R^(1b) are each F.
 33. Thecompound of claim 31, wherein R^(2a) and R^(2b) are each F.
 34. Thecompound of claim 31, wherein B¹ and B² are each —NR^(3c)—; and whereinR^(3c) in —NR^(3c)— is hydrogen or —CH₃.
 35. The compound of claim 34,wherein R^(3c) in —NR^(3c)— is hydrogen.
 36. The compound of claim 31,wherein each R^(6c) and R^(6d) is independently selected from hydrogenand —CH₃.
 37. The compound of claim 31, wherein each R^(5d) and R^(5e)is hydrogen and n is
 0. 38. The compound of claim 31, wherein R^(11a) ishydrogen or —CH₃.
 39. The compound of claim 31, wherein each R^(11b) andR^(11c) is hydrogen.
 40. The compound of claim 31, wherein the phenylazide monomer having the structure of formula (IV) is


41. The compound of claim 31, wherein the zwitterionic monomer havingthe structure of formula (V) comprises sulfobetaine.
 42. The compound ofclaim 31, wherein the zwitterionic monomer having the structure offormula (V) is


43. The compound of claim 31, wherein the random copolymer comprisesperfluorophenylazide methacrylate-co-sulfobetaine methacrylate.
 44. Thecompound of claim 31, wherein the compound is a random copolymer.
 45. Abiofouling resistant coating comprising copolymer of claim
 31. 46. Thebiofouling resistant coating of claim 45, wherein the biofoulingresistant coating is grafted to a surface of a medical device.
 47. Amedical device having a surface grafted with the random copolymer ofclaim
 31. 48. The medical device of claim 47, wherein the medical devicecomprises an implant, an IV, a prosthesis, a suturing material, a valve,a stent, a catheter, a rod, a shunt, a scope, a contact lens, a tubing,a wiring, an electrode, a clip, a fastener, a syringe, a container forstorage of one or more other medical devices, or a combination thereof.49. The medical device of claim 48, wherein the medical device comprisesthe tubing.
 50. The medical device of claim 47, wherein the medicaldevice exhibits reduced bacterial cell adhesion.